Novel compounds

ABSTRACT

Polypeptides and polynucleotides of the genes set forth in Table I and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing polypeptides and polynucleotides of the genes set forth in Table I in diagnostic assays.

FIELD OF INVENTION

[0001] This invention relates to newly identified polypeptides andpolynucleotides encoding such polypeptides, to their use in diagnosisand in identifying compounds that may be agonists, antagonists that arepotentially useful in therapy, and to production of such polypeptidesand polynucleotides. The polynucleotides and polypeptides of the presentinvention also relate to proteins with signal sequences which allow themto be secreted extracellularly or membrane-associated (hereinafter oftenreferred collectively as secreted proteins or secreted polypeptides).

BACKGROUND OF THE INVENTION

[0002] The drug discovery process is currently undergoing a fundamentalrevolution as it embraces “functional genomics”, that is, highthroughput genome- or gene-based biology. This approach as a means toidentify genes and gene products as therapeutic targets is rapidlysuperseding earlier approaches based on “positional cloning”. Aphenotype, that is a biological function or genetic disease, would beidentified and this would then be tracked back to the responsible gene,based on its genetic map position.

[0003] Functional genomics relies heavily on high-throughput DNAsequencing technologies and the various tools of bioinformatics toidentify gene sequences of potential interest from the many molecularbiology databases now available. There is a continuing need to identifyand characterise further genes and their related polypeptides/proteins,as targets for drug discovery.

[0004] Proteins and polypeptides that are naturally secreted into blood,lymph and other body fluids, or secreted into the cellular membrane areof primary interest for pharmaceutical research and development. Thereason for this interest is the relative ease to target proteintherapeutics into their place of action (body fluids or the cellularmembrane). The natural pathway for protein secretion into extracellularspace is the endoplasmic reticulum in eukaryotes and the inner membranein prokaryotes (Palade, 1975, Science, 189, 347; Milstein, Brownlee,Harrison, and Mathews, 1972, Nature New Biol., 239, 117; Blobel, andDobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand, there isno known natural pathway for exporting a protein from the exterior ofthe cells into the cytosol (with the exception of pinocytosis, amechanism of snake venom toxipn-itrusion into cells). Thereforetargeting protein therapeutics into cells poses extreme difficulties.

[0005] The secreted and membrane-associated proteins include but are notlimited to all peptide hormones and their receptors (including but notlimited to insulin, growth hormones, chemokines, cytokines,neuropeptides, integrins, kallikreins, lamins, melanins, natriuretichormones, neuropsin, neurotropins, pituitiary hormones, pleiotropins,prostaglandins, secretogranins, selectins, thromboglobulins, thymosins),the breast and colon cancer gene products, leptin, the obesity geneprotein and its receptors, serum albumin, superoxide dismutase,spliceosome proteins, 7TM (transmembrane) proteins also called asG-protein coupled receptors, immunoglobulins, several families of serineproteinases (including but not limited to proteins of the bloodcoagulation cascade, digestive enzymes), deoxyribonuclease I, etc.

[0006] Therapeutics based on secreted or membrane-associated proteinsapproved by FDA or foreign agencies include but are not limited toinsulin, glucagon, growth hormone, chorionic gonadotropin, folliclestimulating hormone, luteinizing hormone, calcitonin,adrenocorticotropic hormone (ACTH), vasopressin, interleukines,interferones, immunoglobulins, lactoferrin (diverse products marketed byseveral companies), tissue-type plasminogen activator (Alteplase byGenentech), hyaulorindase (Wydase by Wyeth-Ayerst), dornase alpha(Pulmozyme by Genentech), Chymodiactin (chymopapain by Knoll),alglucerase (Ceredase by Genzyme), streptokinase (Kabikinase byPharmacia) (Streptase by Astra), etc. This indicates that secreted andmembrane-associated proteins have an established, proven history astherapeutic targets. Clearly, there is a need for identification andcharacterization of further secreted and membrane-associated proteinswhich can play a role in preventing, ameliorating or correctingdysfunction or disease, including but not limited to diabetes, breast-,prostate-, colon cancer and other malignant tumors, hyper- andhypotension, obesity, bulimia, anorexia, growth abnormalities, asthma,manic depression, dementia, delirium, mental retardation, Huntington'sdisease, Tourette's syndrome, schizophrenia, growth, mental or sexualdevelopment disorders, and dysfunctions of the blood cascade systemincluding those leading to stroke. The proteins of the present inventionwhich include the signal sequences are also useful to further elucidatethe mechanism of protein transport which at present is not entirelyunderstood, and thus can be used as research tools.

SUMMARY OF THE INVENTION

[0007] The present invention relates to particular polypeptides andpolynucleotides of the genes set forth in Table I including recombinantmaterials and methods for their production. Such polypeptides andpolynucleotides are of interest in relation to methods of treatment ofcertain diseases, including, but not limited to, the diseases set forthin Tables III and V, hereinafter referred to as “diseases of theinvention”. In a further aspect, the invention relates to methods foridentifying agonists and antagonists (e.g., inhibitors) using thematerials provided by the invention, and treating conditions associatedwith imbalance of polypeptides and/or polynucleotides of the genes setforth in Table I with the identified compounds. In still a furtheraspect, the invention relates to diagnostic assays for detectingdiseases associated with inappropriate activity or levels the genes setforth in Table I. Another aspect of the invention concerns apolynucleotide comprising any of the nucleotide sequences set forth inthe Sequence Listing and a polypeptide comprising a polypeptide encodedby the nucleotide sequence. In another aspect, the invention relates toa polypeptide comprising any of the polypeptide sequences set forth inthe Sequence Listing and recombinant materials and methods for theirproduction. Another aspect of the invention relates to methods for usingsuch polypeptides and polynucleotides. Such uses include the treatmentof diseases, abnormalities and disorders (hereinafter simply referred toas diseases) caused by abnormal expression, production, function and ormetabolism of the genes of this invention, and such diseases are readilyapparent by those skilled in the art from the homology to other proteinsdisclosed for each attached sequence. In still another aspect, theinvention relates to methods to identify agonists and antagonists usingthe materials provided by the invention, and treating conditionsassociated with the imbalance with the identified compounds. Yet anotheraspect of the invention relates to diagnostic assays for detectingdiseases associated with inappropriate activity or levels of thesecreted proteins of the present invention.

DESCRIPTION OF THE INVENTION

[0008] In a first aspect, the present invention relates to polypeptidesthe genes set forth in Table I. Such polypeptides include:

[0009] (a) an isolated polypeptide encoded by a polynucleotidecomprising a sequence set forth in the Sequence Listing, herein whenreferring to polynucleotides or polypeptides of the Sequence Listing, areference is also made to the Sequence Listing referred to in theSequence Listing;

[0010] (b) an isolated polypeptide comprising a polypeptide sequencehaving at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptidesequence set forth in the Sequence Listing;

[0011] (c) an isolated polypeptide comprising a polypeptide sequence setforth in the Sequence Listing;

[0012] (d) an isolated polypeptide having at least 95%, 96%, 97%, 98%,or 99% identity to a polypeptide sequence set forth in the SequenceListing;

[0013] (e) a polypeptide sequence set forth in the Sequence Listing; and

[0014] (f) an isolated polypeptide having or comprising a polypeptidesequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99compared to a polypeptide sequence set forth in the Sequence Listing;

[0015] (g) fragments and variants of such polypeptides in (a) to (f).

[0016] Polypeptides of the present invention are believed to be membersof the gene families set forth in Table II. They are therefore oftherapeutic and diagnostic interest for the reasons set forth in TablesIII and V. The biological properties of the polypeptides andpolynucleotides of the genes set forth in Table I are hereinafterreferred to as “the biological activity” of polypeptides andpolynucleotides of the genes set forth in Table I. Preferably, apolypeptide of the present invention exhibits at least one biologicalactivity of the genes set forth in Table I.

[0017] Polypeptides of the present invention also include variants ofthe aforementioned polypeptides, including all allelic forms and splicevariants. Such polypeptides vary from the reference polypeptide byinsertions, deletions, and substitutions that may be conservative ornon-conservative, or any combination thereof. Particularly preferredvariants are those in which several, for instance from 50 to 30, from 30to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to1 or 1 amino acids are inserted, substituted, or deleted, in anycombination.

[0018] Preferred fragments of polypeptides of the present inventioninclude an isolated polypeptide comprising an amino acid sequence havingat least 30, 50 or 100 contiguous amino acids from an amino acidsequence set forth in the Sequence Listing, or an isolated polypeptidecomprising an amino acid sequence having at least 30, 50 or 100contiguous amino acids truncated or deleted from an amino acid sequenceset forth in the Sequence Listing. Preferred fragments are biologicallyactive fragments that mediate the biological activity of polypeptidesand polynucleotides of the genes set forth in Table I, including thosewith a similar activity or an improved activity, or with a decreasedundesirable activity. Also preferred are those fragments that areantigenic or immunogenic in an animal, especially in a human.

[0019] Fragments of a polypeptide of the invention may be employed forproducing the corresponding full-length polypeptide by peptidesynthesis; therefore, these variants may be employed as intermediatesfor producing the full-length polypeptides of the invention. Apolypeptide of the present invention may be in the form of the “mature”protein or may be a part of a larger protein such as a precursor or afusion protein. It is often advantageous to include an additional aminoacid sequence that contains secretory or leader sequences,pro-sequences, sequences that aid in purification, for instance multiplehistidine residues, or an additional sequence for stability duringrecombinant production.

[0020] Polypeptides of the present invention can be prepared in anysuitable manner, for instance by isolation form naturally occurringsources, from genetically engineered host cells comprising expressionsystems (vide infra) or by chemical synthesis, using for instanceautomated peptide synthesizers, or a combination of such methods. Meansfor preparing such polypeptides are well understood in the art.

[0021] In a further aspect, the present invention relates topolynucleotides of the genes set forth in Table I. Such polynucleotidesinclude:

[0022] (a) an isolated polynucleotide comprising a polynucleotidesequence having at least 95%, 96%, 97%, 98%, or 99% identity to apolynucleotide sequence set forth in the Sequence Listing;

[0023] (b) an isolated polynucleotide comprising a polynucleotide setforth in the Sequence Listing;

[0024] (c) an isolated polynucleotide having at least 95%, 96%, 97%,98%, or 99% identity to a polynucleotide set forth in the SequenceListing;

[0025] (d) an isolated polynucleotide set forth in the Sequence Listing;

[0026] (e) an isolated polynucleotide comprising a polynucleotidesequence encoding a polypeptide sequence having at least 95%, 96%, 97%,98%, or 99% identity to a polypeptide sequence set forth in the SequenceListing;

[0027] (f) an isolated polynucleotide comprising a polynucleotidesequence encoding a polypeptide set forth in the Sequence Listing;

[0028] (g) an isolated polynucleotide having a polynucleotide sequenceencoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or99% identity to a polypeptide sequence set forth in the SequenceListing;

[0029] (h) an isolated polynucleotide encoding a polypeptide set forthin the Sequence Listing;

[0030] (i) an isolated polynucleotide having or comprising apolynucleotide sequence that has an Identity Index of 0.95, 0.96, 0.97,0.98, or 0.99 compared to a polynucleotide sequence set forth in theSequence Listing;

[0031] (j) an isolated polynucleotide having or comprising apolynucleotide sequence encoding a polypeptide sequence that has anIdentity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to apolypeptide sequence set forth in the Sequence Listing; and

[0032] polynucleotides that are fragments and variants of the abovementioned polynucleotides or that are complementary to above mentionedpolynucleotides, over the entire length thereof.

[0033] Preferred fragments of polynucleotides of the present inventioninclude an isolated polynucleotide comprising an nucleotide sequencehaving at least 15, 30, 50 or 100 contiguous nucleotides from a sequenceset forth in the Sequence Listing, or an isolated polynucleotidecomprising a sequence having at least 30, 50 or 100 contiguousnucleotides truncated or deleted from a sequence set forth in theSequence Listing.

[0034] Preferred variants of polynucleotides of the present inventioninclude splice variants, allelic variants, and polymorphisms, includingpolynucleotides having one or more single nucleotide polymorphisms(SNPs).

[0035] Polynucleotides of the present invention also includepolynucleotides encoding polypeptide variants that comprise an aminoacid sequence set forth in the Sequence Listing and in which several,for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5,from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues aresubstituted, deleted or added, in any combination.

[0036] In a further aspect, the present invention providespolynucleotides that are RNA transcripts of the DNA sequences of thepresent invention. Accordingly, there is provided an RNA polynucleotidethat:

[0037] (a) comprises an RNA transcript of the DNA sequence encoding apolypeptide set forth in the Sequence Listing;

[0038] (b) is a RNA transcript of a DNA sequence encoding a polypeptideset forth in the Sequence Listing;

[0039] (c) comprises an RNA transcript of a DNA sequence set forth inthe Sequence Listing; or

[0040] (d) is a RNA transcript of a DNA sequence set forth in theSequence Listing; and RNA polynucleotides that are complementarythereto.

[0041] The polynucleotide sequences set forth in the Sequence Listingshow homology with the polynucleotide sequences set forth in Table II. Apolynucleotide sequence set forth in the Sequence Listing is a cDNAsequence that encodes a polypeptide set forth in the Sequence Listing. Apolynucleotide sequence encoding a polypeptide set forth in the SequenceListing may be identical to a polypeptide encoding a sequence set forthin the Sequence Listing or it may be a sequence other than a sequenceset forth in the Sequence Listing, which, as a result of the redundancy(degeneracy) of the genetic code, also encodes a polypeptide set forthin the Sequence Listing. A polypeptide of a sequence set forth in theSequence Listing is related to other proteins of the gene families setforth in Table II, having homology and/or structural similarity with thepolypeptides set forth in Table II. Preferred polypeptides andpolynucleotides of the present invention are expected to have, interalia, similar biological functions/properties to their homologouspolypeptides and polynucleotides. Furthermore, preferred polypeptidesand polynucleotides of the present invention have at least one activityof the genes set forth in Table I.

[0042] Polynucleotides of the present invention may be obtained usingstandard cloning and screening techniques from a cDNA library derivedfrom mRNA from the tissues set forth in Table IV (see for instance,Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., ColdSpring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)).Polynucleotides of the invention can also be obtained from naturalsources such as genomic DNA libraries or can be synthesized using wellknown and commercially available techniques.

[0043] When polynucleotides of the present invention are used for therecombinant production of polypeptides of the present invention, thepolynucleotide may include the coding sequence for the maturepolypeptide, by itself, or the coding sequence for the maturepolypeptide in reading frame with other coding sequences, such as thoseencoding a leader or secretory sequence, a pre-, or pro- orprepro-protein sequence, or other fusion peptide portions. For example,a marker sequence that facilitates purification of the fused polypeptidecan be encoded. In certain preferred embodiments of this aspect of theinvention, the marker sequence is a hexa-histidine peptide, as providedin the pQE vector (Qiagen, Inc.) and described in Gentz et al., ProcNatl Acad Sci USA (1989) 86:821-824, or is an HA tag. A polynucleotidemay also contain non-coding 5′ and 3′ sequences, such as transcribed,non-translated sequences, splicing and polyadenylation signals, ribosomebinding sites and sequences that stabilize mRNA.

[0044] Polynucleotides that are identical, or have sufficient identityto a polynucleotide sequence set forth in the Sequence Listing, may beused as hybridization probes for cDNA and genomic DNA or as primers fora nucleic acid amplification reaction (for instance, PCR). Such probesand primers may be used to isolate full-length cDNAs and genomic clonesencoding polypeptides of the present invention and to isolate cDNA andgenomic clones of other genes (including genes encoding paralogs fromhuman sources and orthologs and paralogs from other species) that have ahigh sequence similarity to sequences set forth in the Sequence Listing,typically at least 95% identity. Preferred probes and primers willgenerally comprise at least 15 nucleotides, preferably, at least 30nucleotides and may have at least 50, if not at least 100 nucleotides.Particularly preferred probes will have between 30 and 50 nucleotides.Particularly preferred primers will have between 20 and 25 nucleotides.

[0045] A polynucleotide encoding a polypeptide of the present invention,including homologs from other species, may be obtained by a processcomprising the steps of screening a library under stringenthybridization conditions with a labeled probe having a sequence setforth in the Sequence Listing or a fragment thereof, preferably of atleast 15 nucleotides; and isolating full-length cDNA and genomic clonescontaining the polynucleotide sequence set forth in the SequenceListing. Such hybridization techniques are well known to the skilledartisan. Preferred stringent hybridization conditions include overnightincubation at 42° C. in a solution comprising: 50% formamide, 5×SSC (150mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 microgram/ml denatured,sheared salmon sperm DNA; followed by washing the filters in 0.1×SSC atabout 65° C. Thus the present invention also includes isolatedpolynucleotides, preferably with a nucleotide sequence of at least 100,obtained by screening a library under stringent hybridization conditionswith a labeled probe having the sequence set forth in the SequenceListing or a fragment thereof, preferably of at least 15 nucleotides.

[0046] The skilled artisan will appreciate that, in many cases, anisolated cDNA sequence will be incomplete, in that the region coding forthe polypeptide does not extend all the way through to the 5′ terminus.This is a consequence of reverse transcriptase, an enzyme withinherently low “processivity” (a measure of the ability of the enzyme toremain attached to the template during the polymerisation reaction),failing to complete a DNA copy of the mRNA template during first strandcDNA synthesis.

[0047] There are several methods available and well known to thoseskilled in the art to obtain full-length cDNAs, or extend short cDNAs,for example those based on the method of Rapid Amplification of cDNAends (RACE) (see, for example, Frohman et al., Proc Nat Acad Sci USA 85,8998-9002, 1988). Recent modifications of the technique, exemplified bythe Marathon (trade mark) technology (Clontech Laboratories Inc.) forexample, have significantly simplified the search for longer cDNAs. Inthe Marathon (trade mark) technology, cDNAs have been prepared from mRNAextracted from a chosen tissue and an ‘adaptor’ sequence ligated ontoeach end. Nucleic acid amplification (PCR) is then carried out toamplify the “missing” 5′ end of the cDNA using a combination of genespecific and adaptor specific oligonucleotide primers. The PCR reactionis then repeated using ‘nested’ primers, that is, primers designed toanneal within the amplified product (typically an adapter specificprimer that anneals further 3′ in the adaptor sequence and a genespecific primer that anneals further 5′ in the known gene sequence). Theproducts of this reaction can then be analyzed by DNA sequencing and afull-length cDNA constructed either by joining the product directly tothe existing cDNA to give a complete sequence, or carrying out aseparate full-length PCR using the new sequence information for thedesign of the 5′ primer.

[0048] Recombinant polypeptides of the present invention may be preparedby processes well known in the art from genetically engineered hostcells comprising expression systems. Accordingly, in a further aspect,the present invention relates to expression systems comprising apolynucleotide or polynucleotides of the present invention, to hostcells which are genetically engineered with such expression systems andto the production of polypeptides of the invention by recombinanttechniques. Cell-free translation systems can also be employed toproduce such proteins using RNAs derived from the DNA constructs of thepresent invention.

[0049] For recombinant production, host cells can be geneticallyengineered to incorporate expression systems or portions thereof forpolynucleotides of the present invention. Polynucleotides may beintroduced into host cells by methods described in many standardlaboratory manuals, such as Davis et al., Basic Methods in MolecularBiology (1986) and Sambrook et al.(ibid). Preferred methods ofintroducing polynucleotides into host cells include, for instance,calcium phosphate transfection, DEAE-dextran mediated transfection,transvection, micro-injection, cationic lipid-mediated transfection,electroporation, transduction, scrape loading, ballistic introduction orinfection.

[0050] Representative examples of appropriate hosts include bacterialcells, such as Streptococci, Staphylococci, E. coli, Streptomyces andBacillus subtilis cells; fungal cells, such as yeast cells andAspergillus cells; insect cells such as Drosophila S2 and Spodoptera Sf9cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 andBowes melanoma cells; and plant cells.

[0051] A great variety of expression systems can be used, for instance,chromosomal, episomal and virus-derived systems, e.g., vectors derivedfrom bacterial plasmids, from bacteriophage, from transposons, fromyeast episomes, from insertion elements, from yeast chromosomalelements, from viruses such as baculoviruses, papova viruses, such asSV40, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabiesviruses and retroviruses, and vectors derived from combinations thereof,such as those derived from plasmid and bacteriophage genetic elements,such as cosmids and phagemids. The expression systems may containcontrol regions that regulate as well as engender expression. Generally,any system or vector that is able to maintain, propagate or express apolynucleotide to produce a polypeptide in a host may be used. Theappropriate polynucleotide sequence may be inserted into an expressionsystem by any of a variety of well-known and routine techniques, suchas, for example, those set forth in Sambrook et al., (ibid). Appropriatesecretion signals may be incorporated into the desired polypeptide toallow secretion of the translated protein into the lumen of theendoplasmic reticulum, the periplasmic space or the extracellularenvironment. These signals may be endogenous to the polypeptide or theymay be heterologous signals.

[0052] If a polypeptide of the present invention is to be expressed foruse in screening assays, it is generally preferred that the polypeptidebe produced at the surface of the cell. In this event, the cells may beharvested prior to use in the screening assay. If the polypeptide issecreted into the medium, the medium can be recovered in order torecover and purify the polypeptide. If produced intracellularly, thecells must first be lysed before the polypeptide is recovered.

[0053] Polypeptides of the present invention can be recovered andpurified from recombinant cell cultures by well-known methods includingammonium sulfate or ethanol precipitation, acid extraction, anion orcation exchange chromatography, phosphocellulose chromatography,hydrophobic interaction chromatography, affinity chromatography,hydroxylapatite chromatography and lectin chromatography. Mostpreferably, high performance liquid chromatography is employed forpurification. Well known techniques for refolding proteins may beemployed to regenerate active conformation when the polypeptide isdenatured during intracellular synthesis, isolation and/or purification.

[0054] Polynucleotides of the present invention may be used asdiagnostic reagents, through detecting mutations in the associated gene.Detection of a mutated form of a gene is characterized by thepolynucleotides set forth in the Sequence Listing in the cDNA or genomicsequence and which is associated with a dysfunction. Will provide adiagnostic tool that can add to, or define, a diagnosis of a disease, orsusceptibility to a disease, which results from under-expression,over-expression or altered spatial or temporal expression of the gene.Individuals carrying mutations in the gene may be detected at the DNAlevel by a variety of techniques well known in the art.

[0055] Nucleic acids for diagnosis may be obtained from a subject'scells, such as from blood, urine, saliva, tissue biopsy or autopsymaterial. The genomic DNA may be used directly for detection or it maybe amplified enzymatically by using PCR, preferably RT-PCR, or otheramplification techniques prior to analysis. RNA or cDNA may also be usedin similar fashion. Deletions and insertions can be detected by a changein size of the amplified product in comparison to the normal genotype.Point mutations can be identified by hybridizing amplified DNA tolabeled nucleotide sequences of the genes set forth in Table I.Perfectly matched sequences can be distinguished from mismatchedduplexes by RNase digestion or by differences in melting temperatures.DNA sequence difference may also be detected by alterations in theelectrophoretic mobility of DNA fragments in gels, with or withoutdenaturing agents, or by direct DNA sequencing (see, for instance, Myerset al., Science (1985) 230:1242). Sequence changes at specific locationsmay also be revealed by nuclease protection assays, such as RNase and S1protection or the chemical cleavage method (see Cotton et al., Proc NatlAcad Sci USA (1985) 85: 4397-4401).

[0056] An array of oligonucleotides probes comprising polynucleotidesequences or fragments thereof of the genes set forth in Table I can beconstructed to conduct efficient screening of e.g., genetic mutations.Such arrays are preferably high density arrays or grids. Arraytechnology methods are well known and have general applicability and canbe used to address a variety of questions in molecular geneticsincluding gene expression, genetic linkage, and genetic variability,see, for example, M. Chee et al., Science, 274, 610-613 (1996) and otherreferences cited therein.

[0057] Detection of abnormally decreased or increased levels ofpolypeptide or mRNA expression may also be used for diagnosing ordetermining susceptibility of a subject to a disease of the invention.Decreased or increased expression can be measured at the RNA level usingany of the methods well known in the art for the quantitation ofpolynucleotides, such as, for example, nucleic acid amplification, forinstance PCR, RT-PCR, RNase protection, Northern blotting and otherhybridization methods. Assay techniques that can be used to determinelevels of a protein, such as a polypeptide of the present invention, ina sample derived from a host are well-known to those of skill in theart. Such assay methods include radio-immunoassays, competitive-bindingassays, Western Blot analysis and ELISA assays.

[0058] Thus in another aspect, the present invention relates to adiagnostic kit comprising:

[0059] (a) a polynucleotide of the present invention, preferably thenucleotide sequence set forth in the Sequence Listing, or a fragment oran RNA transcript thereof;

[0060] (b) a nucleotide sequence complementary to that of (a);

[0061] (c) a polypeptide of the present invention, preferably thepolypeptide set forth in the Sequence Listing or a fragment thereof; or

[0062] (d) an antibody to a polypeptide of the present invention,preferably to the polypeptide set forth in the Sequence Listing.

[0063] It will be appreciated that in any such kit, (a), (b), (c) or (d)may comprise a substantial component. Such a kit will be of use indiagnosing a disease or susceptibility to a disease, particularlydiseases of the invention, amongst others.

[0064] The polynucleotide sequences of the present invention arevaluable for chromosome localisation studies. The sequences set forth inthe Sequence Listing are specifically targeted to, and can hybridizewith, a particular location on an individual human chromosome. Themapping of relevant sequences to chromosomes according to the presentinvention is an important first step in correlating those sequences withgene associated disease. Once a sequence has been mapped to a precisechromosomal location, the physical position of the sequence on thechromosome can be correlated with genetic map data. Such data are foundin, for example, V. McKusick, Mendelian Inheritance in Man (availableon-line through Johns Hopkins University Welch Medical Library). Therelationship between genes and diseases that have been mapped to thesame chromosomal region are then identified through linkage analysis(co-inheritance of physically adjacent genes). Precise human chromosomallocalisations for a genomic sequence (gene fragment etc.) can bedetermined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, D.,Thomas, P., Weissenbach, J., and Goodfellow, P., (1994) A method forconstructing radiation hybrid maps of whole genomes, Nature Genetics 7,22-28). A number of RH panels are available from Research Genetics(Huntsville, Ala., USA) e.g. the GeneBridge4 RH panel (Hum Mol Genet1996 March;5(3):339-46 A radiation hybrid map of the human genome.Gyapay G. Schmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D,Muselet D, Prud'Homme J F, Dib C, Auffray C, Morissette J, WeissenbachJ, Goodfellow P N). To determine the chromosomal location of a geneusing this panel, 93 PCRs are performed using primers designed from thegene of interest on RH DNAs. Each of these DNAs contains random humangenomic fragments maintained in a hamster background (human/hamsterhybrid cell lines). These PCRs result in 93 scores indicating thepresence or absence of the PCR product of the gene of interest. Thesescores are compared with scores created using PCR products from genomicsequences of known location. This comparison is conducted athttp://www.genome.wi.mit.edu/.

[0065] The polynucleotide sequences of the present invention are alsovaluable tools for tissue expression studies. Such studies allow thedetermination of expression patterns of polynucleotides of the presentinvention which may give an indication as to the expression patterns ofthe encoded polypeptides in tissues, by detecting the mRNAs that encodethem. The techniques used are well known in the art and include in situhydridization techniques to clones arrayed on a grid, such as cDNAmicroarray hybridization (Schena et al, Science, 270, 467-470, 1995 andShalon et al, Genome Res, 6, 639-645, 1996) and nucleotide amplificationtechniques such as PCR. A preferred method uses the TAQMAN (Trade mark)technology available from Perkin Elmer. Results from these studies canprovide an indication of the normal function of the polypeptide in theorganism. In addition, comparative studies of the normal expressionpattern of mRNAs with that of mRNAs encoded by an alternative form ofthe same gene (for example, one having an alteration in polypeptidecoding potential or a regulatory mutation) can provide valuable insightsinto the role of the polypeptides of the present invention, or that ofinappropriate expression thereof in disease. Such inappropriateexpression may be of a temporal, spatial or simply quantitative nature.

[0066] A further aspect of the present invention relates to antibodies.The polypeptides of the invention or their fragments, or cellsexpressing them, can be used as immunogens to produce antibodies thatare immunospecific for polypeptides of the present invention. The term“immunospecific” means that the antibodies have substantially greateraffinity for the polypeptides of the invention than their affinity forother related polypeptides in the prior art.

[0067] Antibodies generated against polypeptides of the presentinvention may be obtained by administering the polypeptides orepitope-bearing fragments, or cells to an animal, preferably a non-humananimal, using routine protocols. For preparation of monoclonalantibodies, any technique which provides antibodies produced bycontinuous cell line cultures can be used. Examples include thehybridoma technique (Kohler, G. and Milstein, C., Nature (1975)256:495497), the trioma technique, the human B-cell hybridoma technique(Kozbor et al., Immunology Today (1983) 4:72) and the EBV-hybridomatechnique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96,Alan R. Liss, Inc., 1985).

[0068] Techniques for the production of single chain antibodies, such asthose described in U.S. Pat. No. 4,946,778, can also be adapted toproduce single chain antibodies to polypeptides of this invention. Also,transgenic mice, or other organisms, including other mammals, may beused to express humanized antibodies.

[0069] The above-described antibodies may be employed to isolate or toidentify clones expressing the polypeptide or to purify the polypeptidesby affinity chromatography. Antibodies against polypeptides of thepresent invention may also be employed to treat diseases of theinvention, amongst others.

[0070] Polypeptides and polynucleotides of the present invention mayalso be used as vaccines. Accordingly, in a further aspect, the presentinvention relates to a method for inducing an immunological response ina mammal that comprises inoculating the mammal with a polypeptide of thepresent invention, adequate to produce antibody and/or T cell immuneresponse, including, for example, cytokine-producing T cells orcytotoxic T cells, to protect said animal from disease, whether thatdisease is already established within the individual or not. Animmunological response in a mammal may also be induced by a methodcomprises delivering a polypeptide of the present invention via a vectordirecting expression of the polynucleotide and coding for thepolypeptide in vivo in order to induce such an immunological response toproduce antibody to protect said animal from diseases of the invention.One way of administering the vector is by accelerating it into thedesired cells as a coating on particles or otherwise. Such nucleic acidvector may comprise DNA, RNA, a modified nucleic acid, or a DNA/RNAhybrid. For use a vaccine, a polypeptide or a nucleic acid vector willbe normally provided as a vaccine formulation (composition). Theformulation may further comprise a suitable carrier. Since a polypeptidemay be broken down in the stomach, it is preferably administeredparenterally (for instance, subcutaneous, intramuscular, intravenous, orintra-dermal injection). Formulations suitable for parenteraladministration include aqueous and non-aqueous sterile injectionsolutions that may contain anti-oxidants, buffers, bacteriostats andsolutes that render the formulation instonic with the blood of therecipient; and aqueous and non-aqueous sterile suspensions that mayinclude suspending agents or thickening agents. The formulations may bepresented in unit-dose or multi-dose containers, for example, sealedampoules and vials and may be stored in a freeze-dried conditionrequiring only the addition of the sterile liquid carrier immediatelyprior to use. The vaccine formulation may also include adjuvant systemsfor enhancing the immunogenicity of the formulation, such as oil-inwater systems and other systems known in the art. The dosage will dependon the specific activity of the vaccine and can be readily determined byroutine experimentation.

[0071] Polypeptides of the present invention have one or more biologicalfunctions that are of relevance in one or more disease states, inparticular the diseases of the invention hereinbefore mentioned. It istherefore useful to identify compounds that stimulate or inhibit thefunction or level of the polypeptide. Accordingly, in a further aspect,the present invention provides for a method of screening compounds toidentify those that stimulate or inhibit the function or level of thepolypeptide. Such methods identify agonists or antagonists that may beemployed for therapeutic and prophylactic purposes for such diseases ofthe invention as hereinbefore mentioned. Compounds may be identifiedfrom a variety of sources, for example, cells, cell-free preparations,chemical libraries, collections of chemical compounds, and naturalproduct mixtures. Such agonists or antagonists so-identified may benatural or modified substrates, ligands, receptors, enzymes, etc., asthe case may be, of the polypeptide; a structural or functional mimeticthereof (see Coligan et al., Current Protocols in Immunology1(2):Chapter 5 (1991)) or a small molecule. Such small moleculespreferably have a molecular weight below 2,000 daltons, more preferablybetween 300 and 1,000 daltons, and most preferably between 400 and 700daltons. It is preferred that these small molecules are organicmolecules.

[0072] The screening method may simply measure the binding of acandidate compound to the polypeptide, or to cells or membranes bearingthe polypeptide, or a fusion protein thereof, by means of a labeldirectly or indirectly associated with the candidate compound.Alternatively, the screening method may involve measuring or detecting(qualitatively or quantitatively) the competitive binding of a candidatecompound to the polypeptide against a labeled competitor (e.g. agonistor antagonist). Further, these screening methods may test whether thecandidate compound results in a signal generated by activation orinhibition of the polypeptide, using detection systems appropriate tothe cells bearing the polypeptide. Inhibitors of activation aregenerally assayed in the presence of a known agonist and the effect onactivation by the agonist by the presence of the candidate compound isobserved. Further, the screening methods may simply comprise the stepsof mixing a candidate compound with a solution containing a polypeptideof the present invention, to form a mixture, measuring an activity ofthe genes set forth in Table I in the mixture, and comparing activity ofthe mixture of the genes set forth in Table I to a control mixture whichcontains no candidate compound.

[0073] Polypeptides of the present invention may be employed inconventional low capacity screening methods and also in high-throughputscreening (HTS) formats. Such HTS formats include not only thewell-established use of 96- and, more recently, 384-well micotiterplates but also emerging methods such as the nanowell method describedby Schullek et al, Anal Biochem., 246, 20-29, (1997).

[0074] Fusion proteins, such as those made from Fc portion andpolypeptide of the genes set forth in Table I, as hereinbeforedescribed, can also be used for high-throughput screening assays toidentify antagonists for the polypeptide of the present invention (seeD. Bennett et al., J Mol Recognition, 8:52-58 (1995); and K. Johanson etal., J Biol Chem, 270(16):9459-9471 (1995)).

[0075] The polynucleotides, polypeptides and antibodies to thepolypeptide of the present invention may also be used to configurescreening methods for detecting the effect of added compounds on theproduction of mRNA and polypeptide in cells. For example, an ELISA assaymay be constructed for measuring secreted or cell associated levels ofpolypeptide using monoclonal and polyclonal antibodies by standardmethods known in the art. This can be used to discover agents that mayinhibit or enhance the production of polypeptide (also called antagonistor agonist, respectively) from suitably manipulated cells or tissues.

[0076] A polypeptide of the present invention may be used to identifymembrane bound or soluble receptors, if any, through standard receptorbinding techniques known in the art. These include, but are not limitedto, ligand binding and crosslinking assays in which the polypeptide islabeled with a radioactive isotope (for instance, ¹²⁵I), chemicallymodified (for instance, biotinylated), or fused to a peptide sequencesuitable for detection or purification, and incubated with a source ofthe putative receptor (cells, cell membranes, cell supernatants, tissueextracts, bodily fluids). Other methods include biophysical techniquessuch as surface plasmon resonance and spectroscopy. These screeningmethods may also be used to identify agonists and antagonists of thepolypeptide that compete with the binding of the polypeptide to itsreceptors, if any. Standard methods for conducting such assays are wellunderstood in the art.

[0077] Examples of antagonists of polypeptides of the present inventioninclude antibodies or, in some cases, oligonucleotides or proteins thatare closely related to the ligands, substrates, receptors, enzymes,etc., as the case may be, of the polypeptide, e.g., a fragment of theligands, substrates, receptors, enzymes, etc.; or a small molecule thatbind to the polypeptide of the present invention but do not elicit aresponse, so that the activity of the polypeptide is prevented.

[0078] Screening methods may also involve the use of transgenictechnology and the genes set forth in Table I. The art of constructingtransgenic animals is well established. For example, the genes set forthin Table I may be introduced through microinjection into the malepronucleus of fertilized oocytes, retroviral transfer into pre- orpost-implantation embryos, or injection of genetically modified, such asby electroporation, embryonic stem cells into host blastocysts.Particularly useful transgenic animals are so-called “knock-in” animalsin which an animal gene is replaced by the human equivalent within thegenome of that animal. Knock-in transgenic animals are useful in thedrug discovery process, for target validation, where the compound isspecific for the human target. Other useful transgenic animals areso-called “knock-out” animals in which the expression of the animalortholog of a polypeptide of the present invention and encoded by anendogenous DNA sequence in a cell is partially or completely annulled.The gene knock-out may be targeted to specific cells or tissues, mayoccur only in certain cells or tissues as a consequence of thelimitations of the technology, or may occur in all, or substantiallyall, cells in the animal. Transgenic animal technology also offers awhole animal expression-cloning system in which introduced genes areexpressed to give large amounts of polypeptides of the present invention

[0079] Screening kits for use in the above described methods form afurther aspect of the present invention. Such screening kits comprise:

[0080] (a) a polypeptide of the present invention;

[0081] (b) a recombinant cell expressing a polypeptide of the presentinvention;

[0082] (c) a cell membrane expressing a polypeptide of the presentinvention; or

[0083] (d) an antibody to a polypeptide of the present invention;

[0084] which polypeptide is preferably that set forth in the SequenceListing.

[0085] It will be appreciated that in any such kit, (a), (b), (c) or (d)may comprise a substantial component.

[0086] Glossary

[0087] The following definitions are provided to facilitateunderstanding of certain terms used frequently hereinbefore.

[0088] “Antibodies” as used herein includes polyclonal and monoclonalantibodies, chimeric, single chain, and humanized antibodies, as well asFab fragments, including the products of an Fab or other immunoglobulinexpression library.

[0089] “Isolated” means altered “by the hand of man” from its naturalstate, i.e., if it occurs in nature, it has been changed or removed fromits original environment, or both. For example, a polynucleotide or apolypeptide naturally present in a living organism is not “isolated,”but the same polynucleotide or polypeptide separated from the coexistingmaterials of its natural state is “isolated”, as the term is employedherein. Moreover, a polynucleotide or polypeptide that is introducedinto an organism by transformation, genetic manipulation or by any otherrecombinant method is “isolated” even if it is still present in saidorganism, which organism may be living or non-living.

[0090] “Secreted protein activity or secreted polypeptide activity” or“biological activity of the secreted protein or secreted polypeptide”refers to the metabolic or physiologic function of said secreted proteinincluding similar activities or improved activities or these activitieswith decreased undesirable side-effects. Also included are antigenic andimmunogenic activities of said secreted protein.

[0091] “Secreted protein gene” refers to a polynucleotide comprising anyof the attached nucleotide sequences or allelic variants thereof and/ortheir complements.

[0092] “Polynucleotide” generally refers to any polyribonucleotide (RNA)or polydeoxribonucleotide (DNA), which may be unmodified or modified RNAor DNA. “Polynucleotides” include, without limitation, single- anddouble-stranded DNA, DNA that is a mixture of single- anddouble-stranded regions, single- and double-stranded RNA, and RNA thatis mixture of single- and double-stranded regions, hybrid moleculescomprising DNA and RNA that may be single-stranded or, more typically,double-stranded or a mixture of single- and double-stranded regions. Inaddition, “polynucleotide” refers to triple-stranded regions comprisingRNA or DNA or both RNA and DNA. The term “polynucleotide” also includesDNAs or RNAs containing one or more modified bases and DNAs or RNAs withbackbones modified for stability or for other reasons. “Modified” basesinclude, for example, tritylated bases and unusual bases such asinosine. A variety of modifications may be made to DNA and RNA; thus,“polynucleotide” embraces chemically, enzymatically or metabolicallymodified forms of polynucleotides as typically found in nature, as wellas the chemical forms of DNA and RNA characteristic of viruses andcells. “Polynucleotide” also embraces relatively short polynucleotides,often referred to as oligonucleotides.

[0093] “Polypeptide” refers to any polypeptide comprising two or moreamino acids joined to each other by peptide bonds or modified peptidebonds, i.e., peptide isosteres. “Polypeptide” refers to both shortchains, commonly referred to as peptides, oligopeptides or oligomers,and to longer chains, generally referred to as proteins. Polypeptidesmay contain amino acids other than the 20 gene-encoded amino acids.“Polypeptides” include amino acid sequences modified either by naturalprocesses, such as post-translational processing, or by chemicalmodification techniques that are well known in the art. Suchmodifications are well described in basic texts and in more detailedmonographs, as well as in a voluminous research literature.Modifications may occur anywhere in a polypeptide, including the peptidebackbone, the amino acid side-chains and the amino or carboxyl termini.It will be appreciated that the same type of modification may be presentto the same or varying degrees at several sites in a given polypeptide.Also, a given polypeptide may contain many types of modifications.Polypeptides may be branched as a result of ubiquitination, and they maybe cyclic, with or without branching. Cyclic, branched and branchedcyclic polypeptides may result from post-translation natural processesor may be made by synthetic methods. Modifications include acetylation,acylation, ADP-ribosylation, amidation, biotinylation, covalentattachment of flavin, covalent attachment of a heme moiety, covalentattachment of a nucleotide or nucleotide derivative, covalent attachmentof a lipid or lipid derivative, covalent attachment ofphosphotidylinositol, crosslinking, cyclization, disulfide bondformation, demethylation, formation of covalent crosslinks, formation ofcystine, formation of pyroglutamate, formylation, gamma-carboxylation,glycosylation, GPI anchor formation, hydroxylation, iodination,methylation, myristoylation, oxidation, proteolytic processing,phosphorylation, prenylation, racemization, selenoylation, sulfation,transfer-RNA mediated addition of amino acids to proteins such asarginylation, and ubiquitination (see, for instance, Proteins—Structureand Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman andCompany, New York, 1993; Wold, F., Post-translational ProteinModifications: Perspectives and Prospects, 1-12, in Post-translationalCovalent Modification of Proteins, B. C. Johnson, Ed., Academic Press,New York, 1983; Seifter et al., “Analysis for protein modifications andnonprotein cofactors”, Meth Enzymol, 182, 626-646, 1990, and Rattan etal., “Protein Synthesis: Post-translational Modifications and Aging”,Ann NY Acad Sci, 663, 48-62, 1992).

[0094] “Fragment” of a polypeptide sequence refers to a polypeptidesequence that is shorter than the reference sequence but that retainsessentially the same biological function or activity as the referencepolypeptide. “Fragment” of a polynucleotide sequence refers to apolynucleotide sequence that is shorter than the reference sequence setforth in the Sequence Listing.

[0095] “Variant” refers to a polynucleotide or polypeptide that differsfrom a reference polynucleotide or polypeptide, but retains theessential properties thereof. A typical variant of a polynucleotidediffers in nucleotide sequence from the reference polynucleotide.Changes in the nucleotide sequence of the variant may or may not alterthe amino acid sequence of a polypeptide encoded by the referencepolynucleotide. Nucleotide changes may result in amino acidsubstitutions, additions, deletions, fusions and truncations in thepolypeptide encoded by the reference sequence, as discussed below. Atypical variant of a polypeptide differs in amino acid sequence from thereference polypeptide. Generally, alterations are limited so that thesequences of the reference polypeptide and the variant are closelysimilar overall and, in many regions, identical. A variant and referencepolypeptide may differ in amino acid sequence by one or moresubstitutions, insertions, deletions in any combination. A substitutedor inserted amino acid residue may or may not be one encoded by thegenetic code. Typical conservative substitutions include Gly, Ala; Val,Ile, Leu; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe and Tyr. Avariant of a polynucleotide or polypeptide may be naturally occurringsuch as an allele, or it may be a variant that is not known to occurnaturally. Non-naturally occurring variants of polynucleotides andpolypeptides may be made by mutagenesis techniques or by directsynthesis. Also included as variants are polypeptides having one or morepost-translational modifications, for instance glycosylation,phosphorylation, methylation, ADP ribosylation and the like. Embodimentsinclude methylation of the N-terminal amino acid, phosphorylations ofserines and threonines and modification of C-terminal glycines.

[0096] “Allele” refers to one of two or more alternative forms of a geneoccurring at a given locus in the genome.

[0097] “Polymorphism” refers to a variation in nucleotide sequence (andencoded polypeptide sequence, if relevant) at a given position in thegenome within a population.

[0098] “Single Nucleotide Polymorphism” (SNP) refers to the occurrenceof nucleotide variability at a single nucleotide position in the genome,within a population. An SNP may occur within a gene or within intergenicregions of the genome. SNPs can be assayed using Allele SpecificAmplification (ASA). For the process at least 3 primers are required. Acommon primer is used in reverse complement to the polymorphism beingassayed. This common primer can be between 50 and 1500 bps from thepolymorphic base. The other two (or more) primers are identical to eachother except that the final 3′ base wobbles to match one of the two (ormore) alleles that make up the polymorphism. Two (or more) PCR reactionsare then conducted on sample DNA, each using the common primer and oneof the Allele Specific Primers.

[0099] “Splice Variant” as used herein refers to cDNA molecules producedfrom RNA molecules initially transcribed from the same genomic DNAsequence but which have undergone alternative RNA splicing. AlternativeRNA splicing occurs when a primary RNA transcript undergoes splicing,generally for the removal of introns, which results in the production ofmore than one mRNA molecule each of that may encode different amino acidsequences. The term splice variant also refers to the proteins encodedby the above cDNA molecules.

[0100] “Identity” reflects a relationship between two or morepolypeptide sequences or two or more polynucleotide sequences,determined by comparing the sequences. In general, identity refers to anexact nucleotide to nucleotide or amino acid to amino acidcorrespondence of the two polynucleotide or two polypeptide sequences,respectively, over the length of the sequences being compared.

[0101] “% Identity”—For sequences where there is not an exactcorrespondence, a “% identity” may be determined. In general, the twosequences to be compared are aligned to give a maximum correlationbetween the sequences. This may include inserting “gaps” in either oneor both sequences, to enhance the degree of alignment. A % identity maybe determined over the whole length of each of the sequences beingcompared (so-called global alignment), that is particularly suitable forsequences of the same or very similar length, or over shorter, definedlengths (so-called local alignment), that is more suitable for sequencesof unequal length.

[0102] “Similarity” is a further, more sophisticated measure of therelationship between two polypeptide sequences. In general, “similarity”means a comparison between the amino acids of two polypeptide chains, ona residue by residue basis, taking into account not only exactcorrespondences between a between pairs of residues, one from each ofthe sequences being compared (as for identity) but also, where there isnot an exact correspondence, whether, on an evolutionary basis, oneresidue is a likely substitute for the other. This likelihood has anassociated “score” from which the “% similarity” of the two sequencescan then be determined.

[0103] Methods for comparing the identity and similarity of two or moresequences are well known in the art. Thus for instance, programsavailable in the Wisconsin Sequence Analysis Package, version 9.1(Devereux J et al, Nucleic Acids Res, 12, 387-395, 1984, available fromGenetics Computer Group, Madison, Wis., USA), for example the programsBESTFIT and GAP, may be used to determine the % identity between twopolynucleotides and the % identity and the % similarity between twopolypeptide sequences. BESTFIT uses the “local homology” algorithm ofSmith and Waterman (J Mol Biol, 147,195-197, 1981, Advances in AppliedMathematics, 2, 482-489, 1981) and finds the best single region ofsimilarity between two sequences. BESTFIT is more suited to comparingtwo polynucleotide or two polypeptide sequences that are dissimilar inlength, the program assuming that the shorter sequence represents aportion of the longer. In comparison, GAP aligns two sequences, findinga “maximum similarity”, according to the algorithm of Neddleman andWunsch (J Mol Biol, 48, 443-453, 1970). GAP is more suited to comparingsequences that are approximately the same length and an alignment isexpected over the entire length. Preferably, the parameters “Gap Weight”and “Length Weight” used in each program are 50 and 3, forpolynucleotide sequences and 12 and 4 for polypeptide sequences,respectively. Preferably, % identities and similarities are determinedwhen the two sequences being compared are optimally aligned.

[0104] Other programs for determining identity and/or similarity betweensequences are also known in the art, for instance the BLAST family ofprograms (Altschul S F et al, J Mol Biol, 215, 403-410, 1990, Altschul SF et al, Nucleic Acids Res., 25:389-3402, 1997, available from theNational Center for Biotechnology Information (NCBI), Bethesda, Md., USAand accessible through the home page of the NCBI atwww.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology,183, 63-99, 1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85,2444-2448, 1988, available as part of the Wisconsin Sequence AnalysisPackage).

[0105] Preferably, the BLOSUM62 amino acid substitution matrix (HenikoffS and Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) isused in polypeptide sequence comparisons including where nucleotidesequences are first translated into amino acid sequences beforecomparison.

[0106] Preferably, the program BESTFIT is used to determine the %identity of a query polynucleotide or a polypeptide sequence withrespect to a reference polynucleotide or a polypeptide sequence, thequery and the reference sequence being optimally aligned and theparameters of the program set at the default value, as hereinbeforedescribed.

[0107] “Identity Index” is a measure of sequence relatedness which maybe used to compare a candidate sequence (polynucleotide or polypeptide)and a reference sequence. Thus, for instance, a candidate polynucleotidesequence having, for example, an Identity Index of 0.95 compared to areference polynucleotide sequence is identical to the reference sequenceexcept that the candidate polynucleotide sequence may include on averageup to five differences per each 100 nucleotides of the referencesequence. Such differences are selected from the group consisting of atleast one nucleotide deletion, substitution, including transition andtransversion, or insertion. These differences may occur at the 5′ or 3′terminal positions of the reference polynucleotide sequence or anywherebetween these terminal positions, interspersed either individually amongthe nucleotides in the reference sequence or in one or more contiguousgroups within the reference sequence. In other words, to obtain apolynucleotide sequence having an Identity Index of 0.95 compared to areference polynucleotide sequence, an average of up to 5 in every 100 ofthe nucleotides of the in the reference sequence may be deleted,substituted or inserted, or any combination thereof, as hereinbeforedescribed. The same applies mutatis mutandis for other values of theIdentity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0108] Similarly, for a polypeptide, a candidate polypeptide sequencehaving, for example, an Identity Index of 0.95 compared to a referencepolypeptide sequence is identical to the reference sequence except thatthe polypeptide sequence may include an average of up to fivedifferences per each 100 amino acids of the reference sequence. Suchdifferences are selected from the group consisting of at least one aminoacid deletion, substitution, including conservative and non-conservativesubstitution, or insertion. These differences may occur at the amino- orcarboxy-terminal positions of the reference polypeptide sequence oranywhere between these terminal positions, interspersed eitherindividually among the amino acids in the reference sequence or in oneor more contiguous groups within the reference sequence. In other words,to obtain a polypeptide sequence having an Identity Index of 0.95compared to a reference polypeptide sequence, an average of up to 5 inevery 100 of the amino acids in the reference sequence may be deleted,substituted or inserted, or any combination thereof, as hereinbeforedescribed. The same applies mutatis mutandis for other values of theIdentity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0109] The relationship between the number of nucleotide or amino aciddifferences and the Identity Index may be expressed in the followingequation:

n _(a) ≦x _(a)−(x _(a) ·I)

[0110] in which:

[0111] n_(a) is the number of nucleotide or amino acid differences,

[0112] x_(a) is the total number of nucleotides or amino acids in asequence set forth in the Sequence Listing,

[0113] I is the Identity Index,

[0114] · is the symbol for the multiplication operator, and

[0115] in which any non-integer product of x_(a) and I is rounded downto the nearest integer prior to subtracting it from x_(a).

[0116] “Homolog” is a generic term used in the art to indicate apolynucleotide or polypeptide sequence possessing a high degree ofsequence relatedness to a reference sequence. Such relatedness may bequantified by determining the degree of identity and/or similaritybetween the two sequences as hereinbefore defined. Falling within thisgeneric term are the terms “ortholog”, and “paralog”. “Ortholog” refersto a polynucleotide or polypeptide that is the functional equivalent ofthe polynucleotide or polypeptide in another species. “Paralog” refersto a polynucleotide or polypeptide that within the same species which isfunctionally similar.

[0117] “Fusion protein” refers to a protein encoded by two, oftenunrelated, fused genes or fragments thereof. In one example, EP-A-0 464533-A discloses fusion proteins comprising various portions of constantregion of immunoglobulin molecules together with another human proteinor part thereof. In many cases, employing an immunoglobulin Fc region asa part of a fusion protein is advantageous for use in therapy anddiagnosis resulting in, for example, improved pharmacokinetic properties[see, e.g., EP-A 0232 262]. On the other hand, for some uses it would bedesirable to be able to delete the Fc part after the fusion protein hasbeen expressed, detected and purified.

[0118] All publications and references, including but not limited topatents and patent applications, cited in this specification are hereinincorporated by reference in their entirety as if each individualpublication or reference were specifically and individually indicated tobe incorporated by reference herein as being fully set forth. Any patentapplication to which this application claims priority is alsoincorporated by reference herein in its entirety in the manner describedabove for publications and references. TABLE I Corresponding GSK NucleicAcid Protein Gene Name Gene ID SEQ ID NO's SEQ ID NO's sbg300828GLY300828 SEQ ID NO: 1 SEQ ID NO: 25 SEQ ID NO: 2 SEQ ID NO: 26sbg290600OLF 290600 SEQ ID NO: 3 SEQ ID NO: 27 sbg224366CALa 224366 SEQID NO: 4 SEQ ID NO: 28 SEQ ID NO: 5 SEQ ID NO: 29 sbg317645CRF 317645SEQ ID NO: 6 SEQ ID NO: 30 sbg323398LYS 323398 SEQ ID NO: 7 SEQ ID NO:31 sbg222729Cda 222729 SEQ ID NO: 8 SEQ ID NO: 32 SEQ ID NO: 9 SEQ IDNO: 33 sbg313227VDCCa 313227 SEQ ID NO: 10 SEQ ID NO: 34 SEQ ID NO: 11SEQ ID NO: 35 sbg327427mia 327427 SEQ ID NO: 12 SEQ ID NO: 36sbg318729proa 318729 SEQ ID NO: 13 SEQ ID NO: 37 SEQ ID NO: 14 SEQ IDNO: 38 sbg263419CARa 263419 SEQ ID NO: 15 SEQ ID NO: 39 SEQ ID NO: 16SEQ ID NO: 40 sbg334109TES 334109 SEQ ID NO: 17 SEQ ID NO: 41 SEQ ID NO:18 SEQ ID NO: 42 sbg323357SRCR sbg323357 SEQ ID NO: 19 SEQ ID NO: 43sbg294576LAPP 294576 SEQ ID NO: 20 SEQ ID NO: 44 sbg320795MMPa 320795SEQ ID NO: 21 SEQ ID NO: 45 SEQ ID NO: 22 SEQ ID NO: 46 sbh312883.PLK312883 SEQ ID NO: 23 SEQ ID NO: 47 sbg66804SPARCra 66804 SEQ ID NO: 24SEQ ID NO: 48

[0119] TABLE II Cell Localization Closest Polynuclotide by (by Gene NameGene Family homology Closest Polypeptide by homology homology)sbg300828- Proteoglycan SC: DJ994D16 Human GROS1-L protein, Secreted GLYSubmitted (20-JAN-2001) gi: 11127638, Kaul, S. C., Sanger Centre,Hinxton, Sugihara, T., Yoshida, A., Cambridgeshire, CB10 1SA, Nomura, H.and Wadhwa, R. UK. Oncogene 19 (32), 3576-3583 (2000) sbg290600-Olfactomedin- SC: BA292C23 Rat neuronal olfactomedin-related SecretedOLF related Submitted by Sanger Centre, ER localized protein precursor,protein Hinxton, Cambridgeshire, CB10 GB: Q62609, Danielson, P. E., 1SA,UK Forss-Petter, S., Battenberg, E. L., deLecea, L., Bloom, F. E., andSutcliffe, J. G., 1994, J. Neurosci. Res. 38: 468-478 sbg224366-Cadherin GB: AC006203 Human cadeherin 20, gi: 10834607, Secreted CALaSubmitted (18-DEC-1998) Kools, P., Van Imschoot, G. and van WhiteheadInstitute/MIT Center Roy, F. Genomics 68 (3), 283-295 for GenomeResearch, 320 (2000) Charles Street, Cambridge, MA 02141, USA sbg317645-C1q-related GB: AC019017 Human C1q-related factor, Secreted CRF factor(CRF) Submitted (28-DEC-1999) GI: 5729785, Berube N G, Swanson WhiteheadInstitute/MIT Center XH, Bertram M J, Kittle J D, for Genome Research,320 Didenko V, Baskin D S, Smith J R Charles Street, Cambridge, MA andPereira-Smith OM., 1999, 02141, USA. Brain Res. Mol. Brain Res. 63:233-240. sbg323398- Lysozyme C GB: Z98304, Human Hydrolase protein-1,Secreted LYS precursor Submitted (12-MAY-1999) geneseqp: Y52597,Submitted by Sanger Centre, Hinxton, INCYTE PHARM INC, Cambridgeshire,CB10 1SA, UK Publication number and date: WO200028045-A2, 18-MAY-00sbg222729- Leukocyte GB: AC012471 Mouse lymphocyte antigen 108 SecretedCda differentiation Submitted (28-OCT-1999) by isoforms, gi: 9887091,Submitted antigen Genome Therapeutics (21-MAR-2000) Department ofCorporation, 100 Beaver Street, Microbiology and Immunology, Waltham, MA02453, USA Vanderbilt University School of Medicine, 1161 21st AveSouth/ AA4206 Medical Center North, Nashville, TN 37232-2363, USAsbg313227- Voltage- GB: AC005342 and Mouse calcium channel Membrane-VDCCa dependent GB: AC005343 alpha2delta, gi: 6753236, bound calciumBoth were submitted (31-JUL- Klugbauer, N., Lacinova, L., channel 1998)by Molecular and Human Marais, E., Hobom, M. and Genetics, BaylorCollege of Hofmann, F., J. Neurosci. 19, 648-691 Medicine, One BaylorPlaza, (1999) Houston, TX 77030, USA sbg327427- Melanoma SC: AL034428Human melanoma derived growth Secreted MIA inhibitory Sanger Centre,Hinxton, regulatory protein precursor, activity Cambridgeshire, CB101SA, UK gi: 2498559 protein Blesch A, Bosserhoff AK, Apfel R, Behl C,Hessdoerfer B, Schmitt A, Jachimczak P, Lottspeich F, Buettner R,Bogdahn U, 1994, Cancer Res. 54: 5695-5701. sbg318729- 2-19 protein GB:AC022471 Human 2-19 protein precursor Secreted proa precursor Submitted(04-FEB-2000) by gi: 2135170 Lita Annenberg Hazen Genome Bione S,Tamanini F, Maestrini E, Sequencing Center, Cold Spring Tribioli C,Poustka A, Torri G, Harbor Laboratory, 1 Bungtown Rivella S, Toniolo D.Road, Cold Spring Harbor, NY Transcriptional organization of a 11724,USA 450-kb region of the human X chromosome in Xq28. Proc Natl Acad SciUSA 1993 Dec 1; 90(23): 10977-81 sbg263419- Carboxypeptidase GB:AC007938 Pig carboxypeptidase A1, Cytosolic CARa A1 Submitted(01-JUL-1999) by gi: 4336196, Submitted (02-JUL- Human Genome Center,1998) by LBBN, CNRS-UPRESA University of Washington, 6033, Faculte desSciences et Box 352145, Seattle, WA Techniques de St. Jerome, 98195,USA. Universite d'Aix-Marseille, Av. Escadrille Normandie Niemen,Marseille 13397, France sbg334109- Testatin GB: AL121894 Mouse testatinprecursor (cystatin 9), Secreted TES precursor Submitted (17-MAR-2000)gi: 6753546 Sanger Centre, Hinxton, Tohonen V, Osterlund C, andCambridgeshire, CB10 1SA, UK. Nordqvist K, 1998, Proc Natl Acad Sci USA95: 14208-13. sbg323357- Scavenger GB: AL161645 Bovine WC1 antigen, gi:26741, Membrane- SRCR receptor Submitted (17-MAR-2000) Wijngaard PL,Metzelaar MJ, bound cysteine-rich Sanger Centre, Hinxton, MacHugh ND,Morrison WI, and (SRCR) Cambridgeshire, CB10 1SA, Clevers HC, 1992, J.Immunol. UK. 149: 3273-3277. sbg294576- Lysosomal JGI: CITB-E1_2568A17Mouse lysosomal acid phosphatase Secreted LAPP acid Joint GenomeInstitute, precursor, gi: 130728, Geier C, von phosphatase Department ofEnergy, USA Figura K, and Pohlmann R, 1991, precursor Biol Chem HoppeSeyler 372: 301-4. sbg320795- Matrix GB: AL158835 Xenopus laevis matrixSecreted MMPa metalloproteinase Submitted (05-MAR-2000)metalloproteinase gene, gi: 3211705, Sanger Centre, Hinxton, Yang, M.,Murray, M. T. and Cambridgeshire, CB10 1SA, UK Kurkinen, M., A novelmatrix metalloproteinase gene (XMMP) encoding vitronectin-like motifs istransiently expressed in Xenopus laevis early embryo development. 1997J. Biol. Chem. 272 (21), 13527-13533 sbh312883.- Proteoglycan GB:AC003967 Chicken cartilage link protein, Secreted PLK link proteinSubmitted (31-DEC-1997) by gi: 130309, Deak, F., Kiss, I., (PLK) HumanGenome Center, Sparks, K. J., Argraves, W. S., Lawrence LivermoreNational Hampikian, G. and Goetinck, P. F, Laboratory, 7000 East Ave.,Proc. Natl. Acad. Sci. U.S.A. 83 Livermore, CA 94551, USA (11),3766-3770 (1986) sbg66804- Sparc-related GB: AL135747 MouseSPARC-related rpotein, Membrane- SPARCra protein Submitted byGenoscope - gi: 5305327 bound Centre National de Sequencage: Submitted(05-Jun-1998) by BP 19191006 EVRY cedex, GeneCraft, Treskowst. 10,France Muenster 48163, Germany.

[0120] TABLE III Associated Gene Name Uses Diseases sbg300828- Anembodiment of the invention is the use of sbg300828GLY, a Cancer, GLYproteoglycan, to control the sequence of ganglion cell differentiationand infection, initial direction of axons and/or the differentiation ofcells during autoimmune development and maintenance of tissueorganization. disorder, Proteoglycans are complex glycoconjugatescontaining a core protein to hematopoietic which a variable number ofglycosaminoglycan chains (such as heparin disorder, wound sulfate,chondroitin sulfate, etc.) are covalently attached (Hassel J. R., Kimurahealing J. H., and Hascall V. C., 1986, Annu. Rev. Biochem. 55:539-567). Interactions disorders, and between negatively chargedglycosaminoglycan chains and molecules such as inflammation. growthfactors are essential for differentiation of cells during developmentand maintenance of tissue organization (Prydz K, and Dalen K T, 2000, JCell Sci 113: 193-205). It has also been reported that in the developingretina a chondroitin sulfate proteoglycan appears to play an essentialrole in controlling the sequence of ganglion cell differentiation andinitial direction of axons (Silver J, 1994, J Neurol 242: S22-4).sbg290600- An embodiment of the invention is the use of sbg290600OLF, aglycoprotein, Cancer, OLF in chemoreception and the central nervoussystem. A close homologue of infection, sbg290600OLF is olfactomedin.Olfactomedin is a glycoprotein, and reacts autoimmune with proteins ofolfactory cilia. It was originally discovered at the mucociliarydisorder, surface of the amphibian olfactory neuroepithelium andsubsequently found hematopoietic throughout the mammalian brain(Danielson, P. E., Forss-Petter, S., disorder, wound Battenberg, E. L.,deLecea, L., Bloom, F. E., and Sutcliffe, J. G., 1994, J. healingNeurosci. Res. 38: 468-478). Its noticeable deposition at thechemosensory disorders, and surface of the olfactory neuroepitheliumsuggests a role for this protein in inflammation. chemoreception (SnyderD A, Rivers A M, Yokoe H, Menco B P, and Anholt RR, 1991, Biochemistry30: 9143-53). The widespread occurrence of olfactomedin among mammaliansalso suggests its new functions in the central nervous system(Karavanich C A, and Anholt R R, 1998, Mol Biol Evol 15: 718-26).sbg224366- An embodiment of the invention is the use of sbg224366CALa, asecreted Infections, CALa protein, in the identification of targets fornew cancer therapies. A close cancers, homologue of sbg224366CALa is themouse cadherin 7 precursor. autoimmune The cadherins are calciumdependent cell adhesion proteins that preferentially disorders, interactwith themselves in a homophilic mannerin connecting cells; wound healingcadherins may contribute to the sorting of heterogeneous cell types andis disorders, and claimed to be involved in tumor progression.(Faulkner-Jones, B. E., hematopoietic Godhino, L. N. M., Pasquini, G.F., Reese, B. E. and Tan, S. S. Cloning And disorders. Expression OfMouse Cadherin-7, A Type-II Cadherin Isolated From the Developing Eye.Molecular and Cellular Neurosciences. Mol. Cell. Neurosci. (1999) Inpress). sbg317645- An embodiment of the invention is the use ofsbg317645CRF in functions of Nervous system CRF the central nervoussystem, particularly the brain and motor functions. A disorder. closehomologue of sbg224366CALa is C1q. C1q is a subunit of the C1 enzymecomplex that activates the serum complement system. It has been shownthat human CRF transcript is expressed at highest levels in the brain,particularly in the brainstem. Similarly, in mouse brain CRF transcriptsare most abundant in areas of the nervous system involved in motorfunction (Berube N G, Swanson X H, Bertram M J, Kittle J D, Didenko V,Baskin D S, Smith JR, and Pereira-Smith O M., 1999, Brain Res. Mol.Brain Res. 63: 233-240). sbg323398- An embodiment of the invention isthe use of sbg323398LYS, a lysozyme, to Cancer, LYS inhance the activityof immunoagents in tissue and body fluids. infection, Lysozymes areoriginally a bacteriolytic defensive agent and has been autoimmuneadapted to serve a digestive function (Qasba P K, Kumar S, 1997, CritRev disorder, Biochem Mol Biol 32: 255-306). It has been suggested thatlysozymes may hematopoietic serve as biomarkers of periodontal diseaseactivity from inflammatory cell disorder, wound origin (Eley B M, andCox S W, 1998, Br Dent J 184: 323-8). healing disorders, andinflammation. sbg222729- An embodiment of the invention is the use ofsbg222729Cda, a Cancer, autoimmune CDa secreted protein, in thediagnosis and treatment of cancer and disorder, wound autoimmunedisorders. A close homologue of sbg222729Cda is healing disorder,leukocyte differentiation antigen CD84 isoform. infections and CD84, amember of the immunoglobulin superfamily, shows high hematopoietichomology with several molecules belonging to the CD2 family of disordersdifferentiation antigens, is proposed to be useful in the diagnosis andtreatment of cancer and autoimmune disorders (Palou E, Pirotto F, SoleJ, Freed J H, Peral B, Vilardell C, Vilella R, Vives J, Gaya A. Genomiccharacterization of CD84 reveals the existence of five isoformsdiffering in their cytoplasmic domains. Tissue Antigens 2000 Feb; 55(2):118-27). sbg313227- An embodiment of the invention is the use ofsbg313227-VDCCa in Cancer, Infections, VDCCa excitation-contractioncoupling, and drug screening for obtaining autoimmune disorders,agonists and antagonists. A close homologue of sbg313227-VDCCa woundhealing is the calcium channel, voltage dependent, alpha2/delta subunit3. disorders and The 1-type calcium channel is composed of foursubunits: alpha-1, hematopoietic alpha-2, beta and gamma. Alpha-2 anddelta forms heterodimers that disorders are disulfide-linked.Alpha2/delta-3 is expressed exclusively in the brain, e.g., in thehippocampus, cerebellum, and cortex, whereas alpha2/delta-2 is found inseveral tissues. sbg327427- An embodiment of the invention is the use ofsbg327427MIA, a Cancer, infection, MIA growth regulating protein, as afuture antitumor therapeutical agent. autoimmune disorder, Closehomologues of sbg327427MIA are melanoma inhibitory hematopoieticdisorder, activity (MIA) proteins. wound healing MIA proteins havegrowth inhibition on melanoma cells in vitro as disorders, and well assome other neuroectodermal tumors, including gliomas. inflammation.(Blesch A, Bosserhoff A K, Apfel R, Behl C, Hessdoerfer B, Schmitt A,Jachimczak P, Lottspeich F, Buettner R, Bogdahn U, 1994, Cancer Res. 54:5695-5701). sbg318729- An embodiment of the invention is the use ofsbg318729PROa, a Cancer, autoimmune PROa secreted protein, in thediagnosis and treatment of diseases of muscle disorders, infections, andbrain tissues. A close homologue of sbg318729PROa is the 2-19 woundhealing protein precursor. disorders and The 2-19 protein maps to Xq28,is highly expressed in muscle and hematopoietic brain, and may beresponsible for muscle or neurological disorders disorders mapped todistal Xq28 (Bione S, Tamanini F, Maestrini E, Tribioli C, Poustka A,Torri G, Rivella S, Toniolo D. Transcriptional organization of a 450-kbregion of the human X chromosome in Xq28. Proc Natl Acad Sci USA 1993Dec 1; 90(23): 10977-81). sbg263419- An embodiment of the invention isthe use of sbg263419CARa in Infections, cancers, CARa antibody-directenzyme pro-drug therapy of viral infections. A close autoimmunedisorders, homologue of sbg263419CARa is human carboxypeptidase A1.wound healing Human carboxypeptidase A1 is useful in antibody-directenzyme disorders and prodrug therapy of viral infections (MOORE J T,OHMSTEDE C and hematopoietic DEV IK, Molecular chimaera for use inenzyme gene therapy —is disorders activated in a target cell to expressa secretable enzyme which cleaves a prodrug outside the cell into acytotoxic or cytostatic agent. Accession Number R97618. PublicationDate: 30-MAY-96). sbg334109- An embodiment of the invention is the useof sbg334109TES in Cancer, infection, TES natural tissue remodelingevents such as bone resorption and embryo autoimmune disorder,implantation and/or tumor formation and metastasis. A closehematopoietic disorder, homologue of sbg334109TES is testatin. woundhealing Testatin is related to a group of cysteine protease inhibitorsknown as disorders, cystatins. Testatins and their target proteases caninduce testis inflammation, and formation in foetal gonads, and may beassociated with tumor infertility formation and metastasis. In addition,it is suggested that they are also involved in natural tissue remodelingevents such as bone resorption and embryo implantation (Tohonen V,Osterlund C, and Nordqvist K, 1998, Proc Natl Acad Sci USA 95:14208-13). sbg323357- An embodiment of the invention is the use ofsbg323357SRCR in Cancer, infection, SRCR receptor-mediated endocytosisof chemically modified lipoproteins and autoimmune disorder, thepathogenesis of atherosclersis. hematopoietic disorder, Close homologuesof sbg323357SRCR are scavenger receptors. wound healing Scavengerreceptors are involved in receptor-mediated endocytosis of disorders,and chemically modified lipoproteins, such as acetylated and oxidizedinflammation LDL, and therefore have been implicated in the pathogenesisof atherosclersis (Adachi H, Tsujimoto M, Arai H, and Inoue K, 1997, JBiol Chem 272: 31217-20). Especially, macrophage scavenger receptorshave been implicated both in the deposition of lipoprotein cholesterolin artery walls during the formation of atherosclerotic plaques and inhost defense against infections (Krieger M, 1992 Trends Biochem Sci 17:141-6). sbg294576- An embodiment of the invention is the use ofsbg294576LAPP in the Cancer, infection, LAPP diagnosis and treatment ofprostatic cancer, osteolysis, Gaucher's autoimsnune disorder, disease ofthe spleen, and hairy cell leukemia. Close homologues of hematopoieticdisorder, sbg294576LAPP are acid phosphatases. wound healing The acidphosphatases have been used as a marker for prostatic cancer, disorders,and have been linked with miscellaneous disorders, notably increasedinflammation, increased osteolysis, Gaucher's disease of spleen, andhairy cell leukemia (Moss osteolysis, and DW, Raymond FD, and Wile DB;1995; Crit Rev Clin Lab Sci 32: 431-67). Gaucher's disease sbg320795- Anembodiment of the invention is the use of sbg320795-MMPa, a Diabeticnephropathy, MMPa secreted protein, in the treatment, prevention, anddiagnosis of diabetic glomerulonephritis, nephropathy,glomerulonephritis, fibrosis, liver cirrhosis, and fibrosis, livercirrhosis metabolic bone diseases such as osteoporosis. A closehomologue of and metabolic bone sbg320795-MMPa is xenopus laevis matrixmetalloproteinase. disease such as Xenopus laevis matrixmetalloproteinase specifically activates pro- osteoporosis gelatinase a,which is involved in extracellular matrix turn-over on the surface ofcells and is involved in the matrix remodeling of blood vessels (Yang,M., Murray, M. T. and Kurkinen, M., A novel matrix metalloproteinasegene (XMMP) encoding vitronectin-like motifs is transiently expressed inXenopus laevis early embryo development. J. Biol. Chem. 272 (21),13527-13533 (1997)). sbh312883- An embodiment of the invention is theuse of sbh312883-PLK to treat Hematopoietic PLK autoimmune diseases suchas insulin dependent diabetes mellitus, disorders, wound multiplesclerosis, autoimmune thyroiditis, uveoretinitis, rheumatoid healingdisorders, viral arthritis, and abnormal inflammatory immune responses.Close and bacterial infection, homologues of sbh312883-PLK areimmunotherapeutic agents. cancer, and Similar peptides have been used asantigen base immunotherapeutic autoimmune diseases agents in hostsafflicted with autoimmune diseases. such as insulin dependent diabetesmellitus, multiple sclerosis, autoimmune thyroiditis, uveoretinitis,rheumatoid arthritis, and abnormal inflammatory immune responsessbg66804- An embodiment of the invention is the use of sbg66804-SPARCra,a Cataractogenesis, SPARCra secreted protein, in remodeling,development, cell turnover, tissue angiogenesis, wound repair, counteradhesion, and antiproliferation. healing, tumors. A close homologue ofsbg66804-SPARCra, is the mouse SPARC- related protein. SPARC (secretedprotein, acidic and rich in cysteine) is a unique matricellularglycoprotein that is expressed by many different types of cells and isassociated with development, remodeling, cell turnover, and tissuerepair. Its principal functions in vitro are counter adhesion andantiproliferation, which proceed via different signaling pathways. SPARChas demonstrated activities in angiogenesis, cataractogenesis, and woundhealing. SPARC has also been identified in tumors. The sequence of SPARChas been highly conserved among species.

[0121] TABLE IV Quantitative, Tissue-specific mRNA expression detectedusing Sybrivian Quantitative, tissue-specific, mRNA expression patternsof the genes were measured using SYBR- Green Quantitative PCR (AppliedBiosystems, Foster City, CA; see Schmittgen T.D. et al., AnalyticalBiochemistry 285:194-204, 2000) and human cDNAs prepared from varioushuman tissues. Gene-specific PCR primers were designed using the firstnucleic acid sequence listed in the Sequence List for each gene. Resultsare presented as the number of copies of each specific gene's mRNAdetected in 1 ng mRNA pool from each tissue. Two replicate mRNAmeasurements were made from each tissue RNA. Tissue-Specific mRNAExpression (copies per ng mRNA; avg. ± range for 2 data points pertissue) Skeletal Intes Spleen Gene Name Brain Heart Lung Liver Kidneymuscle tine lymph Placenta Testis sbg300828- 2513 ± 66  4268 ± 154 4488± 236 4229 ± 250 4801 ± 79  1801 ± 29  2108 ± 138 7431 ± 152 15800 ±14682 ± GLY 364 1152 sbg290600- 5164 ± 119 234 ± 19 266 ± 41  88 ± 13378 ± 43  187 ± 115 177 ± 23 159 ± 31 239 ± 292 ± OLF 27 4 sbg224366-636 ± 34 13 ± 4  6 ± 1 −13 ± 2   20 ± 0  73 ± 16 −1 ± 1  3 ± 1 −1 ± 5 ±CALa 1 2 sbg323398- 142 ± 8  151 ± 2  201 ± 14 61 ± 6 232 ± 23  72 ± 1369 ± 12 176 ± 4  240 ± 4015 ± LYS 0 251 sbg222729- 12 ± 1 50 ± 2 304 ±2  50 ± 8 100 ± 6  145 ± 4  166 ± 4 2703 ± 75  150 ± 133 ± CDa 8 12sbg313227- 28 ± 6  5 ± 3 22 ± 2  6 ± 8  7 ± 2  6 ± 2 1 ± 4 23 ± 1 91 ±419 ± VDCCa 22 15 sbg263419- 26 ± 5 16 ± 3  29 ± 10 −2 ± 6 42 ± 4 143 ±3  3 ± 1 112 ± 11 177 ± 8301 ± CARa 10 627 sbg323357- 131 ± 8  78 ± 7131 ± 20 57 ± 5 193 ± 18 107 ± 3  59 ± 1 178 ± 3  197 ± 181 ± SRCR 50 47sbg294576- 113 ± 10 89 ± 1  67 ± 20 16 ± 1  51 ± 12 91 ± 1 61 ± 14 80 ±1 74 ± 1618 ± LAPP 0 117 sbg320795- 19 ± 0 258 ± 26 2886 ± 114 219 ± 7 367 ± 27 168 ± 19 4232 ± 277 46644 ± 1535 340 ± 4160 ± MMPa 22 205sbg312883- 364 ± 4   3 ± 3  3 ± 0  96 ± 11  8 ± 0  4 ± 2 22 ± 2 −6 ± 4 3± −5 ± PLK 0 7 sbg66804- 296 ± 53 24 ± 0  4 ± 1 457 ± 21  7 ± 0 68 ± 3 9± 1 439 ± 11 128 ± 1037 ± SPARCra 1 17

[0122] TABLE V Additional diseases based on mRNA expression in specifictissues Tissue Expression Additional Diseases Brain Neurological andpsychiatric diseases, including Alzheimers, parasupranuclear palsey,Huntington's disease, myotonic dystrophy, anorexia, depression,schizophrenia, headache, amnesias, anxiety disorders, sleep disorders,multiple sclerosis Heart Cardiovascular diseases, including congestiveheart failure, dilated cardiomyopathy, cardiac arrhythmias, Hodgson'sDisease, myocardial infarction, cardiac arrhythmias Lung Respiratorydiseases, including asthma, Chronic Obstructive Pulmonary Disease,cystic fibrosis, acute bronchitis, adult respiratory distress syndromeLiver Dyslipidemia, hypercholesterolemia, hypertriglyceridemia,cirrhosis, hepatic encephalopathy, fatty hepatocirrhosis, viral andnonviral hepatitis, Type II Diabetes Mellitis, impaired glucosetolerance Kidney Renal diseases, including acute and chronic renalfailure, acute tubular necrosis, cystinuria, Fanconi's Syndrome,glomerulonephritis, renal cell carcinoma, renovascular hypertensionSkeletal Eulenburg's Disease, hypoglycemia, obesity, tendinitis,periodic paralyses, malignant muscle hyperthermia, paramyotoniacongenita, myotonia congenita Intestine Gastrointestinal diseases,including Myotonia congenita, Ileus, Intestinal Obstruction, TropicalSprue, Pseudomembranous Enterocolitis Spleen/lymph Lymphangiectasia,hypersplenism, angiomas, ankylosing spondylitis, Hodgkin's Disease,macroglobulinemia, malignant lymphomas, rheumatoid arthritis PlacentaChoriocarcinoma, hydatidiform mole, placenta previa Testis Testicularcancer, male reproductive diseases, including low testosterone and maleinfertility Pancreas Diabetic ketoacidosis, Type 1 & 2 diabetes,obesity, impaired glucose tolerance

[0123]

1 48 1 2127 DNA Homo sapiens 1 atggcggtac gcgcgttgaa gctgctgaccacactgctgg ctgtcgtggc cgctgcctcc 60 caagccgagg tcgagtccga ggcaggatggggcatggtga cgcctgatct gctcttcgcc 120 gaggggaccg cagcctacgc gcgcggggactggcccgggg tggtcctgag catggaacgg 180 gcgctgcgct cccgggcagc cctccgcgcccttcgcctgc gctgccgcac ccagtgtgcc 240 gccgacttcc cgtgggagct ggaccccgactggtccccca gcccggccca ggcctcgggc 300 gccgccgccc tgcgcgacct gagcttcttcgggggccttc tgcgtcgcgc tgcctgcctg 360 cgccgctgcc tcgggccgcc ggccgcccactcgctcagcg aagagatgga gctggagttc 420 cgcaagcgga gcccctacaa ctacctgcaggtcgcctact tcaagatcaa caagttggag 480 aaagctgttg ctgcagcaca caccttcttcgtgggcaatc ctgagcacat ggaaatgcag 540 cagaacctag actattacca aaccatgtctggagtgaagg aggccgactt caaggatctt 600 gagactcaac cccatatgca agaatttcgactgggagtgc gactctactc agaggaacag 660 ccacaggaag ctgtgcccca cctagaggcggcgctgcaag aatactttgt ggcctatgag 720 gagtgccgtg ccctctgcga agggccctatgactacgatg gctacaacta ccttgagtac 780 aacgctgacc tcttccaggc catcacagatcattacatcc aggtcctcaa ctgtaagcag 840 aactgtgtca cggagcttgc ttcccacccaagtcgagaga agccctttga agacttcctc 900 ccatcgcatt ataattatct gcagtttgcctactataaca agacaatctg ctattgtaat 960 cttccttgtc ttctgaaaat ctatagaaaaaagaagagtg ccaaggagta ccgacagcga 1020 agcctactgg aaaaagaact gcttttcttcgcttatgatg tttttggaat tccctttgtg 1080 gatccggatt catggactcc agaagaagtgattcccaaga gattgcaaga gaaacagaag 1140 tcagaacggg aaacagccgt acgcatctcccaggagattg ggaaccttat gaaggaaatc 1200 gagacccttg tggaagagaa gaccaaggagtcactggatg tgagcagact gacccgggaa 1260 ggtggccccc tgctgtatga aggcatcagtctcaccatga actccaaact cctgaatggt 1320 tcccagcggg tggtgatgga cggcgtaatctctgaccacg agtgtcagga gctgcagaga 1380 ctgaccaatg tggcagcaac ctcaggagatggctaccggg gtcagacctc cccacatact 1440 cccaatgaaa agttctatgg tgtcactgtcttcaaagccc tcaagctggg gcaagaaggc 1500 aaagttcctc tgcagagtgc ccacctgtactacaacgtga cggagaaggt gcggcgcatc 1560 atggagtcct acttccgcct ggatacgcccctctactttt cctactctca tctggtgtgc 1620 cgcactgcca tcgaagaggt ccaggcagagaggaaggatg atagtcatcc agtccacgtg 1680 gacaactgca tcctgaatgc cgagaccctcgtgtgtgtca aagagccccc agcctacacc 1740 ttccgcgact acagcgccat cctttacctaaatggggact tcgatggcgg aaacttttat 1800 ttcactgaac tggatgccaa gaccgtgacggcagaggtgc agcctcagtg tggaagagcc 1860 gtgggattct cttcaggcac tgaaaacccacatggagtga aggctgtcac cagggggcag 1920 cgctgtgcca tcgccctgtg gttcaccctggaccctcgac acagcgagcg ggacagggtg 1980 caggcagatg acctggtgaa gatgctcttcagcccagaag agatggacct ctcccaggag 2040 cagcccctgg atgcccagca gggtccccccgaacctgcac aagagtctct ctcaggcagt 2100 gaatcgaagc ccaaggatga gctatga 21272 2211 DNA Homo sapiens 2 atggcggtac gcgcgttgaa gctgctgacc acactgctggctgtcgtggc cgctgcctcc 60 caagccgagg tcgagtccga ggcaggatgg ggcatggtgacgcctgatct gctcttcgcc 120 gaggggaccg cagcctacgc gcgcggggac tggcccggggtggtcctgag catggaacgg 180 gcgctgcgct cccgggcagc cctccgcgcc cttcgcctgcgctgccgcac ccagtgtgcc 240 gccgacttcc cgtgggagct ggaccccgac tggtcccccagcccggccca ggcctcgggc 300 gccgccgccc tgcgcgacct gagcttcttc gggggccttctgcgtcgcgc tgcctgcctg 360 cgccgctgcc tcgggccgcc ggccgcccac tcgctcagcgaagagatgga gctggagttc 420 cgcaagcgga gcccctacaa ctacctgcag gtcgcctacttcaagatcaa caagttggag 480 aaagctgttg ctgcagcaca caccttcttc gtgggcaatcctgagcacat ggaaatgcag 540 cagaacctag actattacca aaccatgtct ggagtgaaggaggccgactt caaggatctt 600 gagactcaac cccatatgca agaatttcga ctgggagtgcgactctactc agaggaacag 660 ccacaggaag ctgtgcccca cctagaggcg gcgctgcaagaatactttgt ggcctatgag 720 gagtgccgtg ccctctgcga agggccctat gactacgatggctacaacta ccttgagtac 780 aacgctgacc tcttccaggc catcacagat cattacatccaggtcctcaa ctgtaagcag 840 aactgtgtca cggagcttgc ttcccaccca agtcgagagaagccctttga agacttcctc 900 ccatcgcatt ataattatct gcagtttgcc tactataacattgggaatta tacacaggct 960 gttgaatgtg ccaagaccta tcttctcttc ttccccaatgacgaggtgat gaaccaaaat 1020 ttggcctatt atgcagctat gcttggagaa gaacacaccagatccatcgg cccccgtgag 1080 agtgccaagg agtaccgaca gcgaagccta ctggaaaaagaactgctttt cttcgcttat 1140 gatgtttttg gaattccctt tgtggatccg gattcatggactccagaaga agtgattccc 1200 aagagattgc aagagaaaca gaagtcagaa cgggaaacagccgtacgcat ctcccaggag 1260 attgggaacc ttatgaagga aatcgagacc cttgtggaagagaagaccaa ggagtcactg 1320 gatgtgagca gactgacccg ggaaggtggc cccctgctgtatgaaggcat cagtctcacc 1380 atgaactcca aactcctgaa tggttcccag cgggtggtgatggacggcgt aatctctgac 1440 cacgagtgtc aggagctgca gagactgacc aatgtggcagcaacctcagg agatggctac 1500 cggggtcaga cctccccaca tactcccaat gaaaagttctatggtgtcac tgtcttcaaa 1560 gccctcaagc tggggcaaga aggcaaagtt cctctgcagagtgcccacct gtactacaac 1620 gtgacggaga aggtgcggcg catcatggag tcctacttccgcctggatac gcccctctac 1680 ttttcctact ctcatctggt gtgccgcact gccatcgaagaggtccaggc agagaggaag 1740 gatgatagtc atccagtcca cgtggacaac tgcatcctgaatgccgagac cctcgtgtgt 1800 gtcaaagagc ccccagccta caccttccgc gactacagcgccatccttta cctaaatggg 1860 gacttcgatg gcggaaactt ttatttcact gaactggatgccaagaccgt gacggcagag 1920 gtgcagcctc agtgtggaag agccgtggga ttctcttcaggcactgaaaa cccacatgga 1980 gtgaaggctg tcaccagggg gcagcgctgt gccatcgccctgtggttcac cctggaccct 2040 cgacacagcg agcgggacag ggtgcaggca gatgacctggtgaagatgct cttcagccca 2100 gaagagatgg acctctccca ggagcagccc ctggatgcccagcagggtcc ccccgaacct 2160 gcacaagagt ctctctcagg cagtgaatcg aagcccaaggatgagctatg a 2211 3 1437 DNA Homo sapiens 3 atgagtcctc cactgctgaagcttggcgct gtgcttagta ccatggcaat gatctcaaac 60 tggatgtccc aaactctcccatccttggtg ggactgaaca ccacgaggct gtcgactccg 120 gataccttaa ctcagattagtcctaaagaa gggtggcagg tgtacagctc agctcaggat 180 cctgatgggc ggtgcatttgcacagttgtt gctccagaac aaaacctgtg ttcccgggat 240 gccaaaagca ggcaacttcgccaactactg gaaaaggttc agaacatgtc ccagtctatt 300 gaagtcttaa acttgagaactcagagagat ttccaatatg ttttaaaaat ggaaacccaa 360 atgaaagggc tgaaggcaaaatttcggcag attgaagatg atcgaaagac acttatgacc 420 aagcattttc aggagttgaaagagaaaatg gacgagctcc tgcctttgat ccccgtgctg 480 gaacagtaca aaacagatgctaagttaatc acccagttca aggaggaaat aaggaatctg 540 tctgctgtcc tcactggtattcaggaggaa attggtgcct atgactacga ggaactacac 600 caaagagtgc tgagcttggaaacaagactt cgtgactgca tgaaaaagct aacatgtggc 660 aaactgatga aaatcacaggcccagttaca gtcaagacat ctggaacccg atttggtgct 720 tggatgacag accctttagcatctgagaaa aacaacagag tctggtacat ggacagttat 780 actaacaata aaattgttcgtgaatacaaa tcaattgcag actttgtcag tggggctgaa 840 tcaaggacat acaaccttcctttcaagtgg gcaggaacta accatgttgt ctacaatggc 900 tcactctatt ttaacaagtatcagagtaat atcatcatca aatacagctt tgatatgggg 960 agagtgcttg cccaacgaagcctggagtat gctggttttc ataatgttta cccctacaca 1020 tggggtggat tctctgacatcgacctaatg gctgatgaaa tcgggctgtg ggctgtgtat 1080 gcaactaacc agaatgcaggcaatattgtc atcagccaac ttaaccaaga taccttggag 1140 gtgatgaaga gctggagcactggctacccc aagagaagtg caggggaatc tttcatgatc 1200 tgtgggacac tgtatgtcaccaactcccac ttaactggag ccaaggtgta ttattcctat 1260 tccaccaaaa cctccacatatgagtacaca gacattccct tccataacca atactttcac 1320 atatccatgc ttgactacaatgcaagagat cgagctctct atgcctggaa caatggccac 1380 caggtgctgt tcaatgtcacccttttccat atcatcaaga cagaggatga cacatag 1437 4 1770 DNA Homo sapiens 4atgtggactt ctggtagaat gagcaatgca aagaactggc ttggacttgg catgtccttg 60tacttctggg ggctgatgga ccttacgacc accgttctct cggacacccc aacaccacaa 120ggtgaattag aagcactcct gtcagacaag ccacagtcac atcagcggac caagaggagc 180tgggtttgga accagttttt cgttctggaa gagtacactg ggaccgaccc tttgtatgtc 240ggcaagcttc attcagatat ggacagggga gacggatcca tcaaatacat cctctcggga 300gaaggtgctg gcatcgtgtt taccatcgac gacaccactg gagacatcca cgccattcag 360aggctcgacc gagaggaaag agcccagtat actctaaggg ctcaagccct agacaggcgg 420acgggcaggc caatggagcc cgagtcagag ttcatcatca aaattcaaga catcaatgac 480aatgagccca agttcctgga cggaccttat gtggccactg tgccagaaat gtcccctgtg 540ggtacctccg tcatccaagt gacagccaca gatgcagatg acccgaccta cggcaacagt 600gccagggtgg tgtacagcat tcttcagggc cagccatatt tttctgtgga ctctaaaaca 660ggtgtaatta ggacagcgct catgaacatg gacagagaag ccaaagaata ctacgaagtg 720attatccaag ccaaggacat gggagggcag cttggaggat tagctgggac cacaacagtc 780aacatcaccc tctcagatgt caatgataac ccaccccgct ttccccagaa acattaccag 840atgagtgtgt tggaatcagc tccaattagc tccactgtcg ggagagtgtt tgccaaggac 900ttggatgaag gcatcaatgc agagatgaaa tatactattg tggatggaga tggtgcagat 960gcctttgaca ttagcacaga tcccaatttc caagttggta tcataactgt gaagaagccc 1020ctgagttttg aaagcaagaa aagctacacc ttaaaggtgg agggagccaa tcctcaccta 1080gagatgcgtt ttctgaactt gggcccattt caggacacaa caacagtgca catcagtgtg 1140gaagacgtgg acgagccccc tgtgtttgaa cctggctttt actttgtgga ggtgcctgag 1200gatgtggcga ttggaacaac catacagatc atttctgcca aggacccaga tgtgaccaac 1260aactcaatca gatactccat tgatagaagc agtgaccctg gaagattttt ctatgttgac 1320attacaacag gtgccctaat gacagcaaga cccctagacc gggaagaatt ttcttggcat 1380aatatcactg tccttgctat ggaaatgaac aatccctccc aggttggaag tgttcctgtc 1440acaatcaaag tcttagatgt gaatgacaat gctccagagt tccccagatt ctatgaagct 1500tttgtctgtg agaacgccaa ggcaggacag ctgatccaga cagtgagtgc ggtggaccaa 1560gatgacccac gcaatggtca gcatttctac tacagcttgg ctcctgaggc tgctaacaac 1620cccaacttta ccataaggga caaccaaggt aatcaggtgg atggttggct atctgtgctt 1680ttctacagca taggccagct actttgggtt actgtcttat gcaaacagtg tcaaaggcta 1740cctgttccat accagcaggg aggatgttaa 1770 5 2406 DNA Homo sapiens 5atgtggactt ctggtagaat gagcaatgca aagaactggc ttggacttgg catgtccttg 60tacttctggg ggctgatgga ccttacgacc accgttctct cggacacccc aacaccacaa 120ggtgaattag aagcactcct gtcagacaag ccacagtcac atcagcggac caagaggagc 180tgggtttgga accagttttt cgttctggaa gagtacactg ggaccgaccc tttgtatgtc 240ggcaagcttc attcagatat ggacagggga gacggatcca tcaaatacat cctctcggga 300gaaggtgctg gcatcgtgtt taccatcgac gacaccactg gagacatcca cgccattcag 360aggctcgacc gagaggaaag agcccagtat actctaaggg ctcaagccct agacaggcgg 420acgggcaggc caatggagcc cgagtcagag ttcatcatca aaattcaaga catcaatgac 480aatgagccca agttcctgga cggaccttat gtggccactg tgccagaaat gtcccctgtg 540ggtacctccg tcatccaagt gacagccaca gatgcagatg acccgaccta cggcaacagt 600gccagggtgg tgtacagcat tcttcagggc cagccatatt tttctgtgga ctctaaaaca 660ggtgtaatta ggacagcgct catgaacatg gacagagaag ccaaagaata ctacgaagtg 720attatccaag ccaaggacat gggagggcag cttggaggat tagctgggac cacaacagtg 780aacatcaccc tctcagatgt caatgataac ccaccccgct ttccccagaa acattaccag 840atgagtgtgt tggaatcagc tccaattagc tccactgtcg ggagagtgtt tgccaaggac 900ttggatgaag gcatcaatgc agagatgaaa tatactattg tggatggaga tggtgcagat 960gcctttgaca ttagcacaga tcccaatttc caagttggta tcataactgt gaagaagccc 1020ctgagttttg aaagcaagaa aagctacacc ttaaaggtgg agggagccaa tcctcaccta 1080gagatgcgtt ttctgaactt gggcccattt caggacacaa caacagtgca catcagtgtg 1140gaagacgtgg acgagccccc tgtgtttgaa cctggctttt actttgtgga ggtgcctgag 1200gatgtggcga ttggaacaac catacagatc atttctgcca aggacccaga tgtgaccaac 1260aactcaatca gatactccat tgatagaagc agtgaccctg gaagattttt ctatgttgac 1320attacaacag gtgccctaat gacagcaaga cccctagacc gggaagaatt ttcttggcat 1380aatatcactg tccttgctat ggaaatgaac aatccctccc aggttggaag tgttcctgtc 1440acaatcaaag tcttagatgt gaatgacaat gctccagagt tccccagatt ctatgaagct 1500tttgtctgtg agaacgccaa ggcaggacag ctgatccaga cagtgagtgc ggtggaccaa 1560gatgacccac gcaatggtca gcatttctac tacagcttgg ctcctgaggc tgctaacaac 1620cccaacttta ccataaggga caaccaagat aacacagcac ggattctaac caggaggtct 1680ggtttccggc agcaggagca gagtgtcttt cacctgccta tcctgatagc agatagcggg 1740cagcccgtgc tgagcagcac aggcacactg accatccaag tgtgcagctg tgatgacgac 1800ggccacgtca tgtcctgcag cccagaggcc tacatgctcc cagtcagttt gagccggggc 1860gccctcattg ccatcctcgc ctgcatcttt gtcctcttag tgctggtgtt gctcattttg 1920tccatgaggc ggcaccggaa acaaccatac atcatcgacg acgaggaaaa catccacgag 1980aacatcgtcc gctacgacga cgagggcggc ggcgaggagg acaccgaggc cttcgacatc 2040gcggccatgt ggaacccccg ggaggcgcag gcgggggccg cccccaagac gcggcaggac 2100atgctgcccg agatcgagag cctctcccgc tacgtgcctc agacgtgcgc agtgaacagc 2160actgtccaca gctacgtgct ggccaagctc tacgaggccg acatggacct gtgggcaccg 2220cccttcgact ccctccagac gtatatgttc gagggggacg gctctgtggc ggggtcgctg 2280agctccctgc agtcggccac gtcggactcg gaacagagct tcgacttcct gacggactgg 2340gggccccgct tccggaagct ggccgagctc tacggggcgt cggagggacc cgcgccgctg 2400tggtga 2406 6 864 DNA Homo sapiens 6 atggcactgg ggctgctgat cgcggtgcctctgctgctgc aggcggcgcc ccccggagcg 60 gctcactacg agatgctggg cacctgccgcatgatctgtg acccatacag cgtcgctccc 120 gcagggggac ccgcgggcgc caaggctccaccgccgggac ccagtaccgc tgccctggaa 180 gttatgcagg acctcagcgc caaccccccgcctccgttta tccagggacc aaagggtgat 240 ccggggcgac caggcaagcc agggcctcggggtcctcctg gagagccagg gcctcctggg 300 cccaggggtc ccccgggaga gaaaggagactcggggaggc cagggctacc cggactgcag 360 ttgacaacca gcgcggccgg tggcgttggagtggtgagtg gcggaaccgg gggcggtggc 420 gacacggagg gagaagtgac cagtgcgctgagcgccgcct tcagcggtcc caagatcgcc 480 ttctacgtgg gactcaagag cccccacgaaggctacgagg tgctcaagtt cgacgacgtg 540 gtcaccaatc ttggcaatca ctacgaccccactacaggca agttcagctg ccaggtgcgg 600 ggcatctact tcttcacgta ccacattctcatgcgtggcg gcgacggaac cagcatgtgg 660 gcggatctct gcaagaacgg gcaggtgcgagccagcgcca tagcccagga cgcggaccag 720 aattacgact acgccagcaa cagcgtggtactgcacctgg attcaggcga tgaagtctac 780 gtgaagctgg acggcgggaa ggctcacggcggcaacaata acaagtacag cacgttctcg 840 ggcttcctcc tgtatccgga ttag 864 7480 DNA Homo sapiens 7 atgaaggcct ggggcactgt ggtagtgacc ttggccacgctgatggttgt cactgtggat 60 gccaagatct atgaacgctg cgagctggcg gcaagactggagagagcagg gctgaacggc 120 tacaagggct acggcgttgg agactggctg tgcatggctcattatgagag tggctttgac 180 accgccttcg tggaccacaa tcctgatggc agcagtgaatatggcatttt ccaactgaat 240 tctgcctggt ggtgtgacaa tggcattaca cccaccaagaacctctgcca catggattgt 300 catgacctgc tcaatcgcca tattctggat gacatcaggtgtgccaagca gattgtgtcc 360 tcacagaatg ggctttctgc ctggacttct tggaggctacactgttctgg ccatgattta 420 tctgaatggc tcaaggggtg tgatatgcat gtgaaaattgatccaaaaat tcatccatga 480 8 663 DNA Homo sapiens 8 atggtcagga acatttttaaaacctttcct tctgtgttta cagggaatgt agtttcacaa 60 agcagcttaa ccccattgatggtgaacggg attctggggg agtcagtaac tcttcccctg 120 gagtttcctg caggagagaaggtcaacttc atcacttggc ttttcaatga aacatctctt 180 gccttcatag taccccatgaaaccaaaagt ccagaaatcc acgtgactaa tccgaaacag 240 ggaaagcgac tgaacttcacccagtcctac tccctgcaac tcagcaacct gaagatggaa 300 gacacaggct cttacagagcccagatatcc acaaagacct ctgcaaagct gtccagttac 360 actctgagga tattaagacaactgaggaac atacaagtta ccaatcacag tcagctattt 420 cagaatatga cctgtgagctccatctgact tgctctgtgg aggatgcaga tgacaatgtc 480 tcattcagat gggaggccttgggaaacaca ctttcaagtc agccaaacct cactgtctcc 540 tgggacccca ggatttccagtgaacaggac tacacctgca tagcagagaa tgctgtcagt 600 aatttatcct tctctgtctctgcccagaag ctttgcgaag gtaacagcct gcctcaggtc 660 tga 663 9 1041 DNA Homosapiens 9 atgactgcct caaggtctca agcaccagtc ttcaccgcgg aaagcatgttgtggctgttc 60 caatcgctcc tgtttgtctt ctgctttggc ccagggaatg tagtttcacaaagcagctta 120 accccattga tggtgaacgg gattctgggg gagtcagtaa ctcttcccctggagtttcct 180 gcaggagaga aggtcaactt catcacttgg cttttcaatg aaacatctcttgccttcata 240 gtaccccatg aaaccaaaag tccagaaatc cacgtgacta atccgaaacagggaaagcga 300 ctgaacttca cccagtccta ctccctgcaa ctcagcaacc tgaagatggaagacacaggc 360 tcttacagag cccagatatc cacaaagacc tctgcaaagc tgtccagttacactctgagg 420 atattaagac aactgaggaa catacaagtt accaatcaca gtcagctatttcagaatatg 480 acctgtgagc tccatctgac ttgctctgtg gaggatgcag atgacaatgtctcattcaga 540 tgggaggcct tgggaaacac actttcaagt cagccaaacc tcactgtctcctgggacccc 600 aggatttcca gtgaacagga ctacacctgc atagcagaga atgctgtcagtaatttatcc 660 ttctctgtct ctgcccagaa gctttgcgaa gatgttaaaa ttcaatatacagataccaaa 720 atgattctgt ttatggtttc tgggatatgc atagtcttcg gtttcatcatactgctgtta 780 cttgttttga ggaaaagaag agattcccta tctttgtcta ctcagcgaacacagggcccc 840 gagtccgcaa ggaacctaga gtatgtttca gtgtctccaa cgaacaacactgtgtatgct 900 tcagtcactc attcaaacag ggaaacagaa atctggacac ctagagaaaatgatactatc 960 acaatttact ccacaattaa tcattccaaa gagagtaaac ccactttttccagggcaact 1020 gcccttgaca atgtcgtgta a 1041 10 3228 DNA Homo sapiens 10atgggcacgg cttatctctg ctgtcctcaa gtgctcctcc tcctctgcct gccccggaga 60gtgaagctat gggctgacac cttcggcggg gacctgtata acactgtgac caaatactca 120ggctctctct tgctgcagaa gaagtacaag gatgtggagt ccagtctgaa gatcgaggag 180gtggatggct tggagctggt gaggaagttc tcagaggaca tggagaacat gctgcggagg 240aaagtcgagg cggtccagaa tctggtggaa gctgccgagg aggccgacct gaaccacgaa 300ttcaatgaat ccctggtgtt cgactattac aactcggtcc tgatcaacga gagggacgag 360aagggcaact tcgtggagct gggcgccgag ttcctcctgg agtccaatgc tcacttcagc 420aacctgccgg tgaacacctc catcagcagc gtgcagctgc ccaccaacgt gtacaacaaa 480gacccagata ttttaaatgg agtctacatg tctgaagcct tgaatgctgt cttcgtggag 540aacttccaga gagacccaac gttgacctgg caatattttg gcagtgcaac tggattcttc 600aggatctatc caggtataaa atggacacct gatgagaatg gagtcattac ttttgactgc 660cgaaaccgcg gctggtacat tcaagctgct acttctccca aggacatagt gattttggtg 720gacgtgagcg gcagtatgaa ggggctgagg atgactattg ccaagcacac catcaccacc 780atcttggaca ccctggggga gaatgacttc attaatatca tagcgtacaa tgactacgtc 840cattacatcg agccttgttt taaagggatc ctcgtccagg cggaccgaga caatcgagag 900catttcaaac tgctggtgga ggagttgatg gtcaaaggtg tgggggtcgt ggaccaagcc 960ctgagagaag ccttccagat cctgaagcag ttccaagagg ccaagcaagg aagcctctgc 1020aaccaggcca tcatgctcat cagcgacggc gccgtggagg actacgagcc ggtgtttgag 1080aagtataact ggccagactg taaggtccga gttttcactt acctcattgg gagagaagtg 1140tcttttgctg accgcatgaa gtggattgca tgcaacaaca aaggctacta cacgcagatc 1200tcaacgctgg cggacaccca ggagaacgtg atggaatacc tgcacgtgct cagccgcccc 1260atggtcatca accacgacca cgacatcatc tggacagagg cctacatgga cagcaagctc 1320ctcagctcgc aggctcagag cctgacactg ctcaccactg tggccatgcc agtcttcagc 1380aagaagaacg aaacgcgatc ccatggcatt ctcctgggtg tggtgggctc agatgtggcc 1440ctgagagagc tgatgaagct ggcgccccgg tacaagcttg gagtgcacgg atacgccttt 1500ctgaacacca acaatggcta catcctctcc catcccgacc tccggcccct gtacagagag 1560gggaagaaac taaaacccaa acctaactac aacagtgtgg atctctccga agtggagtgg 1620gaagaccagg ctgaatctct gagaacagcc atgatcaata gggaaacagg tactctctcg 1680atggatgtga aggttccgat ggataaaggg aagcgagttc ttttcctgac caatgactac 1740ttcttcacgg acatcagcga cacccctttc agtttggggg tggtgctgtc ccggggccac 1800ggagaataca tccttctggg gaacacgtct gtggaagaag gcctgcatga cttgcttcac 1860ccagacctgg ccctggccgg tgactggatc tactgcatca cagatattga cccagaccac 1920cggaagctca gccagctaga ggccatgatc cgcttcctca ccaggaagga cccagacctg 1980gagtgtgacg aggagctggt ccgggaggtg ctgtttgacg cggtggtgac agcccccatg 2040gaagcctact ggacagcgct ggccctcaac atgtccgagg agtctgaaca cgtggtggac 2100atggccttcc tgggcacccg ggctggcctc ctgagaagca gcttgttcgt gggctccgag 2160aaggtctccg acaggaagtt cctgacacct gaggacgagg ccagcgtgtt caccctggac 2220cgcttcccgc tgtggtaccg ccaggcctca gagcatcctg ctggcagctt cgtcttcaac 2280ctccgctggg cagaaggacc agaaagtgcg ggtgaaccca tggtggtgac ggcaagcaca 2340gctgtggcgg tgaccgtgga caagaggaca gccattgctg cagccgcggg cgtccaaatg 2400aagctggaat tcctccagcg caaattctgg gcggcaacgc ggcagtgcag cactgtggat 2460gggccgtgca cacagagctg cgaggacagt gatctggact gcttcgtcat cgacaacaac 2520gggttcattc tgatctccaa gaggtcccga gagacgggaa gatttctggg ggaggtggat 2580ggtgctgtcc tgacccagct gctcagcatg ggggtgttca gccaagtgac tatgtatgac 2640tatcaggcca tgtgcaaacc ctcgagtcac caccacagtg cagcccagcc cctggtcagc 2700ccaatttctg ccttcttgac ggcgaccagg tggctgctgc aggagctggt gctgttcctg 2760ctggagtgga gtgtctgggg ctcctggtac gacagagggg ccgaggccca caaacacaag 2820aagcaggacc cgctgcagcc ctgcgacacg gagtaccccg tgttcgtgta ccagccggcc 2880atccgggagg ccaacgggat cgtggagtgc gggccctgcc agaaggtatt tgtggtgcag 2940cagattccca acagtaacct cctcctcctg gtgacagacc ccaccttctg cagaatgggc 3000tccggtcctg agatattgac cttaacagtg gcttctgcac ataatgcctc tgtcaaatgt 3060gaccggatgc gctcccagaa gctccgccgg cgaccagact cctgccacgc cttccatcca 3120gaggagaatg cccaggactg cggcggcgcc tcggacacct cagcctcgcc gcccctactc 3180ctgctgcctg tgtgtgcctg ggggctactg ccccaactcc tgcggtga 3228 11 3345 DNAHomo sapiens 11 atgcctgcaa ctcccaactt cctcgcaaac cccagctcca gcagccgctggattcccctc 60 cagccaatgc ccgtggcctg ggcctttgtg cagaagacct cggccctcctgtggctgctg 120 cttctaggca cctccctgtc ccctgcgtgg ggacaggcca agattcctctggaaacagtg 180 aagctatggg ctgacacctt cggcggggac ctgtataaca ctgtgaccaaatactcaggc 240 tctctcttgc tgcagaagaa gtacaaggat gtggagtcca gtctgaagatcgaggaggtg 300 gatggcttgg agctggtgag gaagttctca gaggacatgg agaacatgctgcggaggaaa 360 gtcgaggcgg tccagaatct ggtggaagct gccgaggagg ccgacctgaaccacgaattc 420 aatgaatccc tggtgttcga ctattacaac tcggtcctga tcaacgagagggacgagaag 480 ggcaacttcg tggagctggg cgccgagttc ctcctggagt ccaatgctcacttcagcaac 540 ctgccggtga acacctccat cagcagcgtg cagctgccca ccaacgtgtacaacaaagac 600 ccagatattt taaatggagt ctacatgtct gaagccttga atgctgtcttcgtggagaac 660 ttccagagag acccaacgtt gacctggcaa tattttggca gtgcaactggattcttcagg 720 atctatccag gtataaaatg gacacctgat gagaatggag tcattacttttgactgccga 780 aaccgcggct ggtacattca agctgctact tctcccaagg acatagtgattttggtggac 840 gtgagcggca gtatgaaggg gctgaggatg actattgcca agcacaccatcaccaccatc 900 ttggacaccc tgggggagaa tgacttcatt aatatcatag cgtacaatgactacgtccat 960 tacatcgagc cttgttttaa agggatcctc gtccaggcgg accgagacaatcgagagcat 1020 ttcaaactgc tggtggagga gttgatggtc aaaggtgtgg gggtcgtggaccaagccctg 1080 agagaagcct tccagatcct gaagcagttc caagaggcca agcaaggaagcctctgcaac 1140 caggccatca tgctcatcag cgacggcgcc gtggaggact acgagccggtgtttgagaag 1200 tataactggc cagactgtaa ggtccgagtt ttcacttacc tcattgggagagaagtgtct 1260 tttgctgacc gcatgaagtg gattgcatgc aacaacaaag gctactacacgcagatctca 1320 acgctggcgg acacccagga gaacgtgatg gaatacctgc acgtgctcagccgccccatg 1380 gtcatcaacc acgaccacga catcatctgg acagaggcct acatggacagcaagctcctc 1440 agctcgcagg ctcagagcct gacactgctc accactgtgg ccatgccagtcttcagcaag 1500 aagaacgaaa cgcgatccca tggcattctc ctgggtgtgg tgggctcagatgtggccctg 1560 agagagctga tgaagctggc gccccggtac aagcttggag tgcacggatacgcctttctg 1620 aacaccaaca atggctacat cctctcccat cccgacctcc ggcccctgtacagagagggg 1680 aagaaactaa aacccaaacc taactacaac agtgtggatc tctccgaagtggagtgggaa 1740 gaccaggctg aatctctgag aacagccatg atcaataggg aaacaggtactctctcgatg 1800 gatgtgaagg ttccgatgga taaagggaag cgagttcttt tcctgaccaatgactacttc 1860 ttcacggaca tcagcgacac ccctttcagt ttgggggtgg tgctgtcccggggccacgga 1920 gaatacatcc ttctggggaa cacgtctgtg gaagaaggcc tgcatgacttgcttcaccca 1980 gacctggccc tggccggtga ctggatctac tgcatcacag atattgacccagaccaccgg 2040 aagctcagcc agctagaggc catgatccgc ttcctcacca ggaaggacccagacctggag 2100 tgtgacgagg agctggtccg ggaggtgctg tttgacgcgg tggtgacagcccccatggaa 2160 gcctactgga cagcgctggc cctcaacatg tccgaggagt ctgaacacgtggtggacatg 2220 gccttcctgg gcacccgggc tggcctcctg agaagcagct tgttcgtgggctccgagaag 2280 gtctccgaca ggaagttcct gacacctgag gacgaggcca gcgtgttcaccctggaccgc 2340 ttcccgctgt ggtaccgcca ggcctcagag catcctgctg gcagcttcgtcttcaacctc 2400 cgctgggcag aaggaccaga aagtgcgggt gaacccatgg tggtgacggcaagcacagct 2460 gtggcggtga ccgtggacaa gaggacagcc attgctgcag ccgcgggcgtccaaatgaag 2520 ctggaattcc tccagcgcaa attctgggcg gcaacgcggc agtgcagcactgtggatggg 2580 ccgtgcacac agagctgcga ggacagtgat ctggactgct tcgtcatcgacaacaacggg 2640 ttcattctga tctccaagag gtcccgagag acgggaagat ttctgggggaggtggatggt 2700 gctgtcctga cccagctgct cagcatgggg gtgttcagcc aagtgactatgtatgactat 2760 caggccatgt gcaaaccctc gagtcaccac cacagtgcag cccagcccctggtcagccca 2820 atttctgcct tcttgacggc gaccaggtgg ctgctgcagg agctggtgctgttcctgctg 2880 gagtggagtg tctggggctc ctggtacgac agaggggccg aggcccacaaacacaagaag 2940 caggacccgc tgcagccctg cgacacggag taccccgtgt tcgtgtaccagccggccatc 3000 cgggaggcca acgggatcgt ggagtgcggg ccctgccaga aggtatttgtggtgcagcag 3060 attcccaaca gtaacctcct cctcctggtg acagacccca ccttctgcagaatgggctcc 3120 ggtcctgaga tattgacctt aacagtggct tctgcacata atgcctctgtcaaatgtgac 3180 cggatgcgct cccagaagct ccgccggcga ccagactcct gccacgccttccatccagag 3240 gagaatgccc aggactgcgg cggcgcctcg gacacctcag cctcgccgcccctactcctg 3300 ctgcctgtgt gtgcctgggg gctactgccc caactcctgc ggtga 334512 387 DNA Homo sapiens 12 atggcaagaa tattgttact tttcctcccg ggtcttgtggctgtatgtgc tgtgcatgga 60 atatttatgg accgtctagc ttccaagaag ctctgtgcagatgatgagtg tgtctatact 120 atttctctgg ctagtgctca agaagattat aatgccccggactgtagatt cattaacgtt 180 aaaaaagggc agcagatcta tgtgtactca aagctggtaaaagaaaatgg agctggagaa 240 ttttgggctg gcagtgttta tggtgatggc caggacgagatgggagtcgt gggttatttc 300 cccaggaact tggtcaagga acagcgtgtg taccaggaagctaccaagga agttcccacc 360 acggatattg acttcttctg cgagtaa 387 13 648 DNAHomo sapiens 13 atgggtctca cctggatcct agtcaccatc ctcctaggtg gtcctggtgttggccttcct 60 cgaattcagc agttcttcac cagcccagag aactcagtga ctgcagaaccaagggccagg 120 aagtacaaat gcggcctgcc ccagccttgt cctgaagagc acctgagctttcgaatagtc 180 agcggggctg ccaatgtcat cgggcccaag atctgcctcg aggacaagatgctcatgagc 240 agcgtcaaag acaatgtggg ccgtggcctg aacatcgccc tggtgaatggggtcagtggt 300 gagctcctag aagccagagc ctttgacatg tgggctggag atgtcaatgatctcttgaag 360 ttcatccggc cactgcatga aggtaccctg gtgtttgtgg cttcctatgatgatccagct 420 accaagatga atgaagagac caggaagctt ttttctgagc tgggcagcaggaatgccaag 480 gatctagcct tccgtgacag ctgggtgttt gtgggagcca aaggtgtgcagaacaagagc 540 ccctttgagc agcatatgaa gaacagtaag cacaccaaca agtatgagggctggccagag 600 gccctggaga tggaaggctg tatccctcga aggagcatag cgggctag 64814 693 DNA Homo sapiens 14 atgaggttgg caggccccct gcgcatcgtg gccctaatcatcattatggg tctcacctgg 60 atcctagtca ccatcctcct aggtggtcct ggtgttggccttcctcgaat tcagcagttc 120 ttcaccagcc cagagaactc agtgactgca gaaccaagggccaggaagta caaatgcggc 180 ctgccccagc cttgtcctga agagcacctg agctttcgaatagtcagcgg ggctgccaat 240 gtcatcgggc ccaagatctg cctcgaggac aagatgctcatgagcagcgt caaagacaat 300 gtgggccgtg gcctgaacat cgccctggtg aatggggtcagtggtgagct cctagaagcc 360 agagcctttg acatgtgggc tggagatgtc aatgatctcttgaagttcat ccggccactg 420 catgaaggta ccctggtgtt tgtggcttcc tatgatgatccagctaccaa gatgaatgaa 480 gagaccagga agcttttttc tgagctgggc agcaggaatgccaaggatct agccttccgt 540 gacagctggg tgtttgtggg agccaaaggt gtgcagaacaagagcccctt tgagcagcat 600 atgaagaaca gtaagcacac caacaagtat gagggctggccagaggccct ggagatggaa 660 ggctgtatcc ctcgaaggag catagcgggc tag 693 151311 DNA Homo sapiens 15 atgcagggca cccctggagg cgggacgcgc cctgggccatcccccgtgga caggcggaca 60 ctcctggtct tcagctttat cctggcagca gctttgggccaaatgaattt cacaggggac 120 caggttcttc gagtcctggc caaagatgag aagcagctttcacttctcgg ggatctggag 180 ggcctgaaac cccagaaggt ggacttctgg cgtggcccagccaggcccag cctccctgtg 240 gatatgagag ttcctttctc tgaactgaaa gacatcaaagcttatctgga gtctcatgga 300 cttgcttaca gcatcatgat aaaggacatc caggtgctgctggatgagga aagacaggcc 360 atggcgaaat cccgccggct ggagcgcagc accaacagcttcagttactc atcataccac 420 accctggagg agatatatag ctggattgac aactttgtaatggagcattc cgatattgtc 480 tcaaaaattc agattggcaa cagctttgaa aaccagtccattcttgtcct gaagttcagc 540 actggaggtt ctcggcaccc agccatctgg attgacactggaattcactc ccgggagtgg 600 atcacccatg ccaccggcat ctggactgcc aataagattgtcagtgatta tggcaaagac 660 cgtgtcctga cagacatact gaatgccatg gacatcttcatagagctcgt cacaaaccct 720 gatgggtttg cttttaccca cagcatgaac cgcttatggcggaagaacaa gtccatcaga 780 cctggaatct tctgcatcgg cgtggatctc aacaggaactggaagtcggg ttttggagga 840 aatggttcta acagcaaccc ctgctcagaa acttatcacgggccctcccc tcagtcggag 900 ccggaggtgg ctgccatagt gaacttcatc acagcccatggcaacttcaa ggctctgatc 960 tccatccaca gctactctca gatgcttatg tacccttacggccgattgct ggagcccgtt 1020 tcaaatcaga gggagttgta cgatcttgcc aaggatgcggtggaggcctt gtataaggtc 1080 catgggatcg agtacatttt tggcagcatc agcaccaccctctatgtggc cagtgggatc 1140 accgtcgact gggcctatga cagtggcatc aagtacgccttcagctttga gctccgggac 1200 actgggcagt atggcttcct gctgccggcc acacagatcatccccacggc ccaggagacg 1260 tggatggcgc ttcggaccat catggagcac accctgaatcacccctacta g 1311 16 1260 DNA Homo sapiens 16 atgcggacac tcctggtcttcagctttatc ctggcagcag ctttgggcca aatgaatttc 60 acaggggacc aggttcttcgagtcctggcc aaagatgaga agcagctttc acttctcggg 120 gatctggagg gcctgaaaccccagaaggtg gacttctggc gtggcccagc caggcccagc 180 ctccctgtgg atatgagagttcctttctct gaactgaaag acatcaaagc ttatctggag 240 tctcatggac ttgcttacagcatcatgata aaggacatcc aggtgctgct ggatgaggaa 300 agacaggcca tggcgaaatcccgccggctg gagcgcagca ccaacagctt cagttactca 360 tcataccaca ccctggaggagatatatagc tggattgaca actttgtaat ggagcattcc 420 gatattgtct caaaaattcagattggcaac agctttgaaa accagtccat tcttgtcctg 480 aagttcagca ctggaggttctcggcaccca gccatctgga ttgacactgg aattcactcc 540 cgggagtgga tcacccatgccaccggcatc tggactgcca ataagattgt cagtgattat 600 ggcaaagacc gtgtcctgacagacatactg aatgccatgg acatcttcat agagctcgtc 660 acaaaccctg atgggtttgcttttacccac agcatgaacc gcttatggcg gaagaacaag 720 tccatcagac ctggaatcttctgcatcggc gtggatctca acaggaactg gaagtcgggt 780 tttggaggaa atggttctaacagcaacccc tgctcagaaa cttatcacgg gccctcccct 840 cagtcggagc cggaggtggctgccatagtg aacttcatca cagcccatgg caacttcaag 900 gctctgatct ccatccacagctactctcag atgcttatgt acccttacgg ccgattgctg 960 gagcccgttt caaatcagagggagttgtac gatcttgcca aggatgcggt ggaggccttg 1020 tataaggtcc atgggatcgagtacattttt ggcagcatca gcaccaccct ctatgtggcc 1080 agtgggatca ccgtcgactgggcctatgac agtggcatca agtacgcctt cagctttgag 1140 ctccgggaca ctgggcagtatggcttcctg ctgccggcca cacagatcat ccccacggcc 1200 caggagacgt ggatggcgcttcggaccatc atggagcaca ccctgaatca cccctactag 1260 17 360 DNA Homo sapiens17 atgtggagtc tgccgccgag cagggctctg tcctgtgcgc cactgctgct tctcttcagc 60ttccagttcc tggttaccta tgcttggcgt ttccaagagg aagaggagtg gaatgaccaa 120aaacaaattg ctgtttatct ccctcccacc ctggagtttg ccgtgtacac attcaacaag 180cagagcaagg actggtatgc ctacaagctg gtgcctgtcc tggcttcctg gaaggagcag 240gttgatgagc acatcctttt ctgcactagt gtccagcaca ggctgctgag tgatgggcag 300gggtggcagc gtgtggggca gggcttaacc aggactcctg gttcaccatt tgtagtctaa 360 18447 DNA Homo sapiens 18 atgtcgagtc cgcagaggag gaaggctatg ccctgggcactgtcactgct tctcatgggc 60 ttccagctcc tggtgactta tgcctggtgt tctgaagaggaaatgggtgg taataataaa 120 atagtccagg atcctatgtt cctcgccaca gtggagtttgccttgaacac tttcaacgtg 180 cagagcaagg aggagcatgc ctacaggctg ttgcgcgtcctgagttcatg gagggaggat 240 agcatggaca gaaagatggt gttctccatg aatctgcaactgcgccaaac cgtatgtagg 300 aaatttgaag atgacattga caactgccct tttcaagaaagcctggagct gaacaacact 360 ttcacctgct tcttcaccat cagcaccagg ccctggatgactcagttcag cctcctgaac 420 aagacctgct tggagggatt ccactga 447 19 2697 DNAHomo sapiens 19 atgagggcag ctctctggac cctgggactc gggccccttc ttctgaatctctgggcagtc 60 cccattggtg gaccaggtgc tctgaggctg gcgtacagac acagcacgtgcgacggagtg 120 gtgttggtcc gacaccacgg ggcatgggga tacgtgtgca accaggagtggacgctggca 180 gaggcctctg tcgtgtgcag gcagctgggc tgcggccctg ccgtgggcgcccccaagtat 240 gtcccgctgc ctggagagat ggcccagccc tggcttcaca acgtgtcctgccggggcaac 300 gagtcctccc tctgggagtg cagccttggc tcatggtgcc agagcccgtgcccccacgca 360 tgggtggtgg tcgcgctgtg ctccaacggc actttccggg agctccggctggtgaagggc 420 cgcagtccct gcgcgggact ccccgagatc agaaacgtga atggggtggaccgcctctgt 480 gtcctgcatg tggaggaggc catggtgttc tgccgggagc tggggtgcggccctgtgctc 540 caggcccccc gccgggacgt gggcgtcgtc aggaagtacc tggcctgcaggggtaccgag 600 cccaccatcc gcagctgcag actggacaac aacttccgca gcggctgcgacctgcggctg 660 gacgcagagg tggtctgctc aggacacacc gaggcccgac tggtgggcggcgagcacccc 720 tgcgccgggc gcctggaggt gacctggggc accgtctgtg atgcggccctggacctggcc 780 acggcccacg tggtgtgccg ggagctgcag tgtggggcgg tcgtgtccacgcccgagggc 840 gcccgcttcg gccggggctc ggggccggtg tggacggagg ccttccgctgtgcgggcaac 900 gagtcgctgc tgttccactg cccacggggg cgtgggagcc agtgtgggcatggtcacgac 960 gcggggctca ggtgctcaga gttcaggatg gtcaacggca gcagcagctgtgagggccgc 1020 gtggagttcc aggtgcaggg gtcctgggca cccctctgtg ccacccactgggacatagca 1080 gatgccaccg tcctctgcca ccagctcaac tgtggcaacg cggtggccgcacctggagga 1140 ggccattttg gggacgggga cgctgccatc tggcctgatg cctttcactgtgaggggaca 1200 gagtcctact tgtggaattg cccagtaagc accctggggg ccccggcctgtgccccggga 1260 aacacagcct ccgcggtctg ctcaggtctg gcccacgccc tgcgactgagggaaggacag 1320 agccgctgtg acggccgcgt ggaggtctcc ctggatggcg tgtggggccgcgtcctggac 1380 gatgcctggg acctgcgcgg cgcgggcgtg gtgtgccggc aactcgggtgcagaggggcc 1440 cagcaagcct atgacgcacc tgcccccagc cgcggatccg tccaggtggcgctgagccgc 1500 gtgcgctgtc tgggcaccga aacccgcctg actcagtgca acgtgtccgcgaccctgcag 1560 gagcccgcgg ggacctcgcg ggacgccggc gtggtgtgct ccggtgaggtcggaaccgcg 1620 tcccccatgg cccgtcgcca cgggatcccg ggcgccctga ctctgtctctccacagggag 1680 cctcagggtg cggctggccg cggggccggg gcgctgcacg ggggcgcgtggggcaccgtg 1740 tgtgacgatg cctgggacct gcgggacgcg cacgtggtct gcaggcagctgggctgtggc 1800 cgcgccctga gcgccctggg ggccgcacac ttcggagccg gggcagggcgcatctggctg 1860 gacgagctgg gctgccaggg ccacgagtct gcgctgtggc agtgcccgtcggcgggctgg 1920 gggcggcacg actggaggca caaggaggac gccggcgtct tctgctcagagtcggtggct 1980 ctgaggctgc gaggtgggac ctgctgctgt gctgggtggc tggacgtgttctacaatggg 2040 acctggggcg ccatgtgcag caatgccctg aaggacctct ccttgtccatcatctgcaag 2100 cagctggggt gtggggtgtg gggagtgggg ctggctggag aacaggcccttcccctcgcg 2160 ggcaccggga ccgcctgggt ggacaacatc gagtgccgca ggctgcccaactccactctg 2220 tggcaatgcc cttcccaccc atggcacccg cactcttgcg accttcgagagcaggtctgg 2280 attacctgtg cagtgaccgc agcccctttt gcagaggagg gcgcactgcgcgtgcgcggg 2340 ggcgaggacc gctgctccgg gcgcgtggag ctctggcacg cgggctcctggggcaccgtg 2400 tgcgacgatg gctgggacct ggcggacgcg gaggtcgtgt gccgccagctgggctgtggt 2460 cgggccgtcg ccgccctggg ggccgccgcc tttggccctg gctccgggcccgtgtggctg 2520 gacgaggtgg ggtgccgggg cagcgaggcg tccctgtggg gctgccctgcggagcggtgg 2580 ggacgcggag accgcgcgca cgaggaggac gcgggcgtgc gctgctggggtgagtggggg 2640 gcggtgggaa gtcggtcatg gggccggcag agggcgctgg gatggagtcagtcttga 2697 20 1281 DNA Homo sapiens 20 atggccggcc tggggttttggggccaccct gctggacctc tcctgctgct gctgctgctg 60 gtgctgccac cccgggccctgccagaagga cccctggtgt tcgtggctct ggtattccgc 120 catggcgacc gggccccgctggcctcctac cccatggacc cacacaagga ggtggcctcc 180 accctgtggc cacgaggcctgggccagctg accacggagg gggtccgcca gcagctggag 240 ctgggccgct tcctgaggagccgctacgag gccttcctga gtccggagta ccggcgggag 300 gaggtgtaca tccgcagcacggactttgac cgcacgctgg agagtgccca ggccaacctt 360 gccgggctgt ttcccgaggctgctccaggg agccccgagg cccgctggag gccgatcccg 420 gtgcacacgg tgcccgtggctgaggataag ctgctgaggt tccccatgcg cagctgtccc 480 cgataccacg agctgctgcgggaggccacc gaggccgccg agtaccagga ggccctggag 540 ggctggacgg gcttcctgagtcgcctggag aacttcacgg gactgtcgct ggttggagag 600 ccactgcgca gggcatggaaggttctggac accctcatgt gccagcaagc ccacggtctt 660 ccactaccag cctgggcctccccagatgtc ctgcggactc ttgcccagat ctcggctttg 720 gatattggag cccacgtgggcccaccccgg gcagcagaga aggcccagct gacagggggg 780 atcctgctga atgctatccttgcaaacttc tcccgggtcc agcgcctggg gctgcccctc 840 aagatggtca tgtactcagctcatgacagc accctgctgg ccctccaggg ggccctgggc 900 ctctatgatg gacacaccccgccatatgct gcctgcctcg gctttgagtt ccggaagcac 960 ctggggaatc ccgccaaagatggagggaat gtcaccgtct ccctcttcta ccgcaatgac 1020 tccgcccacc tgcccctgcctctcagcctc cccgggtgcc cggccccctg tccactaggc 1080 cgcttctacc agctgactgccccggcccgg cctcccgccc atggggtctc ctgccatggc 1140 ccctatgagg ctgccatccccccagctcca gtggtgcccc tgctggccgg agctgtagct 1200 gtgctggtgg cactcagcttggggctgggc ctgctggcct ggagaccagg gtgcctgcgg 1260 gccttggggg gccccgtgtg a1281 21 1428 DNA Homo sapiens 21 atgctcgccg cctccatctt ccgtccgacactgctgctct gctggctggc tgctccctgg 60 cccacccagc ccgagagtct cttccacagccgggaccgct cggacctgga gccgtcccca 120 ctgcgccagg ccaagcccat tgccgacctccacgctgctc agcggttcct gtccagatac 180 ggctggtcag gggtgtgggc ggcctgggggcccagtcccg aggggccgcc ggagaccccc 240 aagggcgccg ccctggccga ggcggtgcgcaggttccagc gggcgaacgc gctgccggcc 300 agcggggagc tggacgcggc caccctagcggccatgaacc ggccgcgctg cggggtcccg 360 gacatgcgcc caccgccccc ctccgccccgccttcgcccc cgggcccgcc ccccagagcc 420 cgctccaggc gctccccgcg ggcgccgctgtccttgtccc ggcggggttg gcagccccgg 480 ggctaccccg acggcggagc tgcccaggccttctccaaga ggacgctgag ctggcggctg 540 ctgggcgagg ccctgagcag ccaactgtccgtggccgacc agcggcgcat tgtggcgctg 600 gccttcagga tgtggagcga ggtgacgccgctggacttcc gcgaggacct ggccgccccc 660 ggggccgcgg tcgacatcaa gctgggctttgggagaggct cctgtgaggg atcatttgat 720 actgcgtttg actggattcg caaagagagaaaccaatatg gagaggtgat ggtgagattt 780 agcacatatt tcttccgtaa cagctggtactggctttatg aaaatcgaaa caataggaca 840 cgctatgggg accctatcca aatcctcactggctggcctg gaatcccaac acacaacata 900 gatgcctttg ttcacatctg gacatggaaaagagatgaac gttatttttt tcaaggaaat 960 caatactgga gatatgacag tgacaaggatcaggccctca cagaagatga acaaggaaaa 1020 agctatccca aattgatttc agaaggatttcctggcatcc caagtcccct agacacggcg 1080 ttttatgacc gaagacagaa gttaatttacttcttcaagg agtcccttgt atttgcattt 1140 gatgtcaaca gaaatcgagt acttaattcttatccaaaga ggattactga agtttttcca 1200 gcagtaatac cacaaaatca tcctttcagaaatatagatt ccgcttatta ctcctatgca 1260 tacaactcca ttttcttttt caaaggcaatgcatactgga aggtagttaa tgacaaggac 1320 aaacaacaga attcctggct tcctgctaatggcttatttc caaaaaagtt tatttcagag 1380 aagtggtttg atgtttgtga cgtccatatctccacactga acatgtaa 1428 22 1590 DNA Homo sapiens 22 atgctcgccgcctccatctt ccgtccgaca ctgctgctct gctggctggc tgctccctgg 60 cccacccagcccgagagtct cttccacagc cgggaccgct cggacctgga gccgtcccca 120 ctgcgccaggccaagcccat tgccgacctc cacgctgctc agcggttcct gtccagatac 180 ggctggtcaggggtgtgggc ggcctggggg cccagtcccg aggggccgcc ggagaccccc 240 aagggcgccgccctggccga ggcggtgcgc aggttccagc gggcgaacgc gctgccggcc 300 agcggggagctggacgcggc caccctagcg gccatgaacc ggccgcgctg cgggccccgg 360 ggctaccccgacggcggagc tgcccaggcc ttctccaaga ggacgctgag ctggcggctg 420 ctgggcgaggccctgagcag ccaactgtcc gtggccgacc agcggcgcat tgtggcgctg 480 gccttcaggatgtggagcga ggtgacgccg ctggacttcc gcgaggacct ggccgccccc 540 ggggccgcggtcgacatcaa gctgggcttt gggagaggcc ggcacctggg ctgtccgcgg 600 gccttcgatgggagcgggca ggagtttgca cacgcctggc gcctaggtga cattcacttt 660 gacgacgacgagcacttcac acctcccacc agtgacacgg gcatcagcct tctcaaggtg 720 gccgtccatgaaattggcca tgtcctgggc ttgcctcaca cctacaggac gggatccata 780 atgcaaccaaattacattcc ccaggagcct gcctttgagt tggactggtc agacaggaaa 840 gcaattcaaaagctgtatgg ctcctgtgag ggatcatttg atactgcgtt tgactggatt 900 cgcaaagagagaaaccaata tggagaggtg atggtgagat ttagcacata tttcttccgt 960 aacagctggtactggcttta tgaaaatcga aacaatagga cacgctatgg ggaccctatc 1020 caaatcctcactggctggcc tggaatccca acacacaaca tagatgcctt tgttcacatc 1080 tggacatggaaaagagatga acgttatttt tttcaaggaa atcaatactg gagatatgac 1140 agtgacaaggatcaggccct cacagaagat gaacaaggaa aaagctatcc caaattgatt 1200 tcagaaggatttcctggcat cccaagtccc ctagacacgg cgttttatga ccgaagacag 1260 aagttaatttacttcttcaa ggagtccctt gtatttgcat ttgatgtcaa cagaaatcga 1320 gtacttaattcttatccaaa gaggattact gaagtttttc cagcagtaat accacaaaat 1380 catcctttcagaaatataga ttccgcttat tactcctatg catacaactc cattttcttt 1440 ttcaaaggcaatgcatactg gaaggtagtt aatgacaagg acaaacaaca gaattcctgg 1500 cttcctgctaatggcttatt tccaaaaaag tttatttcag agaagtggtt tgatgtttgt 1560 gacgtccatatctccacact gaacatgtaa 1590 23 1209 DNA Homo sapiens 23 atggtgtgcgctcgggcggc cctcggtccc ggcgcgctct gggccgcggc ctggggcgtc 60 ctgctgctcacagcccctgc gggggcgcag cgtggccgga agaaggtcgt gcacgtgctg 120 gagggtgagtcgggctcggt agtggtacag acagcgcctg ggcaggtggt aagccaccgt 180 ggtggcaccatcgtcttgcc ctgccgctac cactatgagg cagccgccca cggtcacgac 240 ggcgtccggctcaagtggac aaaggtggtg gacccgctgg ccttcaccga cgtcttcgtg 300 gcactaggcccccagcaccg ggcattcggc agctaccgtg ggcgggctga gctgcagggc 360 gacgggcctggggatgcctc cctggtcctc cgcaacgtca cgctgcaaga ctacgggcgc 420 tatgagtgcgaagtcaccaa tgagctggaa gatgacgctg gcatggtcaa gctggacctg 480 gaaggcgtggtctttcccta ccacccccgt ggaggccgat acaagctgac cttcgcggag 540 gcgcagcgcgcgtgcgccga gcaggacggc atcctggcat ctgcagaaca gctgcacgcg 600 gcctggcgcgacggcctgga ctggtgcaac gcgggctggt tgcgcgacgg ctcagtgcaa 660 taccccgtgaaccggccccg ggagccctgc ggcggcctgg gggggaccgg gagtgcaggg 720 ggcggcggtgatgccaacgg gggcctgcgc aactacgggt atcgccataa cgccgaggaa 780 cgctacgacgccttctgctt cacgtccaac ctgccggggc gcgtgttctt cctgaagccg 840 ctgcgacctgtacccttctc cggagctgcg cgcgcgtgtg ctgcgcgtgg cgcggccgtg 900 gccaaggtggggcagctgtt cgccgcgtgg aagctgcagc tgctagaccg ctgcaccgcg 960 ggttggctggccgatggcag tgcgcgctac cccatcgtga acccgcgagc gcgctgcgga 1020 ggccgcaggcctggtgtgcg cagcctcggc ttcccggacg ccacccgacg gctcttcggc 1080 gtctactgctaccgcgctcc aggagcaccg gacccggcac ctggcggctg gggctggggc 1140 tgggcgggcggcggcggctg ggcagggggc gcgcgcgatc ctgctgcctg gacccctctg 1200 cacgtctag1209 24 1326 DNA Homo sapiens 24 atgctgcccg cgcgctgcgc ccgcctgctcacgccccact tgctgctggt gttggtgcag 60 ctgtcccctg ctcgcggcca ccgcaccacaggccccaggt ttctaataag tgaccgtgac 120 ccacagtgca acctccactg ctccaggactcaacccaaac ccatctgtgc ctctgatggc 180 aggtcctacg agtccatgtg tgagtaccagcgagccaagt gccgagaccc gaccctgggc 240 gtggtgcatc gaggtagatg caaagatgctggccagagca agtgtcgcct ggagcgggct 300 caagccctgg agcaagccaa gaagcctcaggaagctgtgt ttgtcccaga gtgtggcgag 360 gatggctcct ttacccaggt gcagtgccatacttacactg ggtactgctg gtgtgtcacc 420 ccggatggga agcccatcag tggctcttctgtgcagaata aaactcctgt atgttcaggt 480 tcagtcaccg acaagccctt gagccagggtaactcaggaa ggaaagatga cgggtctaag 540 ccgacaccca cgatggagac ccagccggtgttcgatggag atgaaatcac agccccaact 600 ctatggatta aacacttggt gatcaaggactccaaactga acaacaccaa cataagaaat 660 tcagagaaag tctattcgtg tgaccaggagaggcagagtg ccctggaaga ggcccagcag 720 aatccccgtg agggtattgt catccctgaatgtgcccctg ggggactcta taagccagtg 780 caatgccacc agtccactgg ctactgctggtgtgtgctgg tggacacagg gcgcccgctg 840 cctgggacct ccacacgcta cgtgatgcccagttgtgaga gcgacgccag ggccaagact 900 acagaggcgg atgacccctt caaggacagggagctaccag gctgtccaga agggaagaaa 960 atggagttta tcaccagcct actggatgctctcaccactg acatggttca ggccattaac 1020 tcagcagcgc ccactggagg tgggaggttctcagagccag accccagcca caccctggag 1080 gagcgggtag tgcactggta tttcagccagctggacagca atagcagcaa cgacattaac 1140 aagcgggaga tgaagccctt caagcgctacgtgaagaaga aagccaagcc caagaaatgt 1200 gcccggcgtt tcaccgacta ctgtgacctgaacaaagaca aggtcatttc actgcctgag 1260 ctgaagggct gcctgggtgt tagcaaagaaggtggtagcc ttggcagttt cccccaggca 1320 aaatga 1326 25 708 PRT Homosapiens 25 Met Ala Val Arg Ala Leu Lys Leu Leu Thr Thr Leu Leu Ala ValVal 1 5 10 15 Ala Ala Ala Ser Gln Ala Glu Val Glu Ser Glu Ala Gly TrpGly Met 20 25 30 Val Thr Pro Asp Leu Leu Phe Ala Glu Gly Thr Ala Ala TyrAla Arg 35 40 45 Gly Asp Trp Pro Gly Val Val Leu Ser Met Glu Arg Ala LeuArg Ser 50 55 60 Arg Ala Ala Leu Arg Ala Leu Arg Leu Arg Cys Arg Thr GlnCys Ala 65 70 75 80 Ala Asp Phe Pro Trp Glu Leu Asp Pro Asp Trp Ser ProSer Pro Ala 85 90 95 Gln Ala Ser Gly Ala Ala Ala Leu Arg Asp Leu Ser PhePhe Gly Gly 100 105 110 Leu Leu Arg Arg Ala Ala Cys Leu Arg Arg Cys LeuGly Pro Pro Ala 115 120 125 Ala His Ser Leu Ser Glu Glu Met Glu Leu GluPhe Arg Lys Arg Ser 130 135 140 Pro Tyr Asn Tyr Leu Gln Val Ala Tyr PheLys Ile Asn Lys Leu Glu 145 150 155 160 Lys Ala Val Ala Ala Ala His ThrPhe Phe Val Gly Asn Pro Glu His 165 170 175 Met Glu Met Gln Gln Asn LeuAsp Tyr Tyr Gln Thr Met Ser Gly Val 180 185 190 Lys Glu Ala Asp Phe LysAsp Leu Glu Thr Gln Pro His Met Gln Glu 195 200 205 Phe Arg Leu Gly ValArg Leu Tyr Ser Glu Glu Gln Pro Gln Glu Ala 210 215 220 Val Pro His LeuGlu Ala Ala Leu Gln Glu Tyr Phe Val Ala Tyr Glu 225 230 235 240 Glu CysArg Ala Leu Cys Glu Gly Pro Tyr Asp Tyr Asp Gly Tyr Asn 245 250 255 TyrLeu Glu Tyr Asn Ala Asp Leu Phe Gln Ala Ile Thr Asp His Tyr 260 265 270Ile Gln Val Leu Asn Cys Lys Gln Asn Cys Val Thr Glu Leu Ala Ser 275 280285 His Pro Ser Arg Glu Lys Pro Phe Glu Asp Phe Leu Pro Ser His Tyr 290295 300 Asn Tyr Leu Gln Phe Ala Tyr Tyr Asn Lys Thr Ile Cys Tyr Cys Asn305 310 315 320 Leu Pro Cys Leu Leu Lys Ile Tyr Arg Lys Lys Lys Ser AlaLys Glu 325 330 335 Tyr Arg Gln Arg Ser Leu Leu Glu Lys Glu Leu Leu PhePhe Ala Tyr 340 345 350 Asp Val Phe Gly Ile Pro Phe Val Asp Pro Asp SerTrp Thr Pro Glu 355 360 365 Glu Val Ile Pro Lys Arg Leu Gln Glu Lys GlnLys Ser Glu Arg Glu 370 375 380 Thr Ala Val Arg Ile Ser Gln Glu Ile GlyAsn Leu Met Lys Glu Ile 385 390 395 400 Glu Thr Leu Val Glu Glu Lys ThrLys Glu Ser Leu Asp Val Ser Arg 405 410 415 Leu Thr Arg Glu Gly Gly ProLeu Leu Tyr Glu Gly Ile Ser Leu Thr 420 425 430 Met Asn Ser Lys Leu LeuAsn Gly Ser Gln Arg Val Val Met Asp Gly 435 440 445 Val Ile Ser Asp HisGlu Cys Gln Glu Leu Gln Arg Leu Thr Asn Val 450 455 460 Ala Ala Thr SerGly Asp Gly Tyr Arg Gly Gln Thr Ser Pro His Thr 465 470 475 480 Pro AsnGlu Lys Phe Tyr Gly Val Thr Val Phe Lys Ala Leu Lys Leu 485 490 495 GlyGln Glu Gly Lys Val Pro Leu Gln Ser Ala His Leu Tyr Tyr Asn 500 505 510Val Thr Glu Lys Val Arg Arg Ile Met Glu Ser Tyr Phe Arg Leu Asp 515 520525 Thr Pro Leu Tyr Phe Ser Tyr Ser His Leu Val Cys Arg Thr Ala Ile 530535 540 Glu Glu Val Gln Ala Glu Arg Lys Asp Asp Ser His Pro Val His Val545 550 555 560 Asp Asn Cys Ile Leu Asn Ala Glu Thr Leu Val Cys Val LysGlu Pro 565 570 575 Pro Ala Tyr Thr Phe Arg Asp Tyr Ser Ala Ile Leu TyrLeu Asn Gly 580 585 590 Asp Phe Asp Gly Gly Asn Phe Tyr Phe Thr Glu LeuAsp Ala Lys Thr 595 600 605 Val Thr Ala Glu Val Gln Pro Gln Cys Gly ArgAla Val Gly Phe Ser 610 615 620 Ser Gly Thr Glu Asn Pro His Gly Val LysAla Val Thr Arg Gly Gln 625 630 635 640 Arg Cys Ala Ile Ala Leu Trp PheThr Leu Asp Pro Arg His Ser Glu 645 650 655 Arg Asp Arg Val Gln Ala AspAsp Leu Val Lys Met Leu Phe Ser Pro 660 665 670 Glu Glu Met Asp Leu SerGln Glu Gln Pro Leu Asp Ala Gln Gln Gly 675 680 685 Pro Pro Glu Pro AlaGln Glu Ser Leu Ser Gly Ser Glu Ser Lys Pro 690 695 700 Lys Asp Glu Leu705 26 736 PRT Homo sapiens 26 Met Ala Val Arg Ala Leu Lys Leu Leu ThrThr Leu Leu Ala Val Val 1 5 10 15 Ala Ala Ala Ser Gln Ala Glu Val GluSer Glu Ala Gly Trp Gly Met 20 25 30 Val Thr Pro Asp Leu Leu Phe Ala GluGly Thr Ala Ala Tyr Ala Arg 35 40 45 Gly Asp Trp Pro Gly Val Val Leu SerMet Glu Arg Ala Leu Arg Ser 50 55 60 Arg Ala Ala Leu Arg Ala Leu Arg LeuArg Cys Arg Thr Gln Cys Ala 65 70 75 80 Ala Asp Phe Pro Trp Glu Leu AspPro Asp Trp Ser Pro Ser Pro Ala 85 90 95 Gln Ala Ser Gly Ala Ala Ala LeuArg Asp Leu Ser Phe Phe Gly Gly 100 105 110 Leu Leu Arg Arg Ala Ala CysLeu Arg Arg Cys Leu Gly Pro Pro Ala 115 120 125 Ala His Ser Leu Ser GluGlu Met Glu Leu Glu Phe Arg Lys Arg Ser 130 135 140 Pro Tyr Asn Tyr LeuGln Val Ala Tyr Phe Lys Ile Asn Lys Leu Glu 145 150 155 160 Lys Ala ValAla Ala Ala His Thr Phe Phe Val Gly Asn Pro Glu His 165 170 175 Met GluMet Gln Gln Asn Leu Asp Tyr Tyr Gln Thr Met Ser Gly Val 180 185 190 LysGlu Ala Asp Phe Lys Asp Leu Glu Thr Gln Pro His Met Gln Glu 195 200 205Phe Arg Leu Gly Val Arg Leu Tyr Ser Glu Glu Gln Pro Gln Glu Ala 210 215220 Val Pro His Leu Glu Ala Ala Leu Gln Glu Tyr Phe Val Ala Tyr Glu 225230 235 240 Glu Cys Arg Ala Leu Cys Glu Gly Pro Tyr Asp Tyr Asp Gly TyrAsn 245 250 255 Tyr Leu Glu Tyr Asn Ala Asp Leu Phe Gln Ala Ile Thr AspHis Tyr 260 265 270 Ile Gln Val Leu Asn Cys Lys Gln Asn Cys Val Thr GluLeu Ala Ser 275 280 285 His Pro Ser Arg Glu Lys Pro Phe Glu Asp Phe LeuPro Ser His Tyr 290 295 300 Asn Tyr Leu Gln Phe Ala Tyr Tyr Asn Ile GlyAsn Tyr Thr Gln Ala 305 310 315 320 Val Glu Cys Ala Lys Thr Tyr Leu LeuPhe Phe Pro Asn Asp Glu Val 325 330 335 Met Asn Gln Asn Leu Ala Tyr TyrAla Ala Met Leu Gly Glu Glu His 340 345 350 Thr Arg Ser Ile Gly Pro ArgGlu Ser Ala Lys Glu Tyr Arg Gln Arg 355 360 365 Ser Leu Leu Glu Lys GluLeu Leu Phe Phe Ala Tyr Asp Val Phe Gly 370 375 380 Ile Pro Phe Val AspPro Asp Ser Trp Thr Pro Glu Glu Val Ile Pro 385 390 395 400 Lys Arg LeuGln Glu Lys Gln Lys Ser Glu Arg Glu Thr Ala Val Arg 405 410 415 Ile SerGln Glu Ile Gly Asn Leu Met Lys Glu Ile Glu Thr Leu Val 420 425 430 GluGlu Lys Thr Lys Glu Ser Leu Asp Val Ser Arg Leu Thr Arg Glu 435 440 445Gly Gly Pro Leu Leu Tyr Glu Gly Ile Ser Leu Thr Met Asn Ser Lys 450 455460 Leu Leu Asn Gly Ser Gln Arg Val Val Met Asp Gly Val Ile Ser Asp 465470 475 480 His Glu Cys Gln Glu Leu Gln Arg Leu Thr Asn Val Ala Ala ThrSer 485 490 495 Gly Asp Gly Tyr Arg Gly Gln Thr Ser Pro His Thr Pro AsnGlu Lys 500 505 510 Phe Tyr Gly Val Thr Val Phe Lys Ala Leu Lys Leu GlyGln Glu Gly 515 520 525 Lys Val Pro Leu Gln Ser Ala His Leu Tyr Tyr AsnVal Thr Glu Lys 530 535 540 Val Arg Arg Ile Met Glu Ser Tyr Phe Arg LeuAsp Thr Pro Leu Tyr 545 550 555 560 Phe Ser Tyr Ser His Leu Val Cys ArgThr Ala Ile Glu Glu Val Gln 565 570 575 Ala Glu Arg Lys Asp Asp Ser HisPro Val His Val Asp Asn Cys Ile 580 585 590 Leu Asn Ala Glu Thr Leu ValCys Val Lys Glu Pro Pro Ala Tyr Thr 595 600 605 Phe Arg Asp Tyr Ser AlaIle Leu Tyr Leu Asn Gly Asp Phe Asp Gly 610 615 620 Gly Asn Phe Tyr PheThr Glu Leu Asp Ala Lys Thr Val Thr Ala Glu 625 630 635 640 Val Gln ProGln Cys Gly Arg Ala Val Gly Phe Ser Ser Gly Thr Glu 645 650 655 Asn ProHis Gly Val Lys Ala Val Thr Arg Gly Gln Arg Cys Ala Ile 660 665 670 AlaLeu Trp Phe Thr Leu Asp Pro Arg His Ser Glu Arg Asp Arg Val 675 680 685Gln Ala Asp Asp Leu Val Lys Met Leu Phe Ser Pro Glu Glu Met Asp 690 695700 Leu Ser Gln Glu Gln Pro Leu Asp Ala Gln Gln Gly Pro Pro Glu Pro 705710 715 720 Ala Gln Glu Ser Leu Ser Gly Ser Glu Ser Lys Pro Lys Asp GluLeu 725 730 735 27 478 PRT Homo sapiens 27 Met Ser Pro Pro Leu Leu LysLeu Gly Ala Val Leu Ser Thr Met Ala 1 5 10 15 Met Ile Ser Asn Trp MetSer Gln Thr Leu Pro Ser Leu Val Gly Leu 20 25 30 Asn Thr Thr Arg Leu SerThr Pro Asp Thr Leu Thr Gln Ile Ser Pro 35 40 45 Lys Glu Gly Trp Gln ValTyr Ser Ser Ala Gln Asp Pro Asp Gly Arg 50 55 60 Cys Ile Cys Thr Val ValAla Pro Glu Gln Asn Leu Cys Ser Arg Asp 65 70 75 80 Ala Lys Ser Arg GlnLeu Arg Gln Leu Leu Glu Lys Val Gln Asn Met 85 90 95 Ser Gln Ser Ile GluVal Leu Asn Leu Arg Thr Gln Arg Asp Phe Gln 100 105 110 Tyr Val Leu LysMet Glu Thr Gln Met Lys Gly Leu Lys Ala Lys Phe 115 120 125 Arg Gln IleGlu Asp Asp Arg Lys Thr Leu Met Thr Lys His Phe Gln 130 135 140 Glu LeuLys Glu Lys Met Asp Glu Leu Leu Pro Leu Ile Pro Val Leu 145 150 155 160Glu Gln Tyr Lys Thr Asp Ala Lys Leu Ile Thr Gln Phe Lys Glu Glu 165 170175 Ile Arg Asn Leu Ser Ala Val Leu Thr Gly Ile Gln Glu Glu Ile Gly 180185 190 Ala Tyr Asp Tyr Glu Glu Leu His Gln Arg Val Leu Ser Leu Glu Thr195 200 205 Arg Leu Arg Asp Cys Met Lys Lys Leu Thr Cys Gly Lys Leu MetLys 210 215 220 Ile Thr Gly Pro Val Thr Val Lys Thr Ser Gly Thr Arg PheGly Ala 225 230 235 240 Trp Met Thr Asp Pro Leu Ala Ser Glu Lys Asn AsnArg Val Trp Tyr 245 250 255 Met Asp Ser Tyr Thr Asn Asn Lys Ile Val ArgGlu Tyr Lys Ser Ile 260 265 270 Ala Asp Phe Val Ser Gly Ala Glu Ser ArgThr Tyr Asn Leu Pro Phe 275 280 285 Lys Trp Ala Gly Thr Asn His Val ValTyr Asn Gly Ser Leu Tyr Phe 290 295 300 Asn Lys Tyr Gln Ser Asn Ile IleIle Lys Tyr Ser Phe Asp Met Gly 305 310 315 320 Arg Val Leu Ala Gln ArgSer Leu Glu Tyr Ala Gly Phe His Asn Val 325 330 335 Tyr Pro Tyr Thr TrpGly Gly Phe Ser Asp Ile Asp Leu Met Ala Asp 340 345 350 Glu Ile Gly LeuTrp Ala Val Tyr Ala Thr Asn Gln Asn Ala Gly Asn 355 360 365 Ile Val IleSer Gln Leu Asn Gln Asp Thr Leu Glu Val Met Lys Ser 370 375 380 Trp SerThr Gly Tyr Pro Lys Arg Ser Ala Gly Glu Ser Phe Met Ile 385 390 395 400Cys Gly Thr Leu Tyr Val Thr Asn Ser His Leu Thr Gly Ala Lys Val 405 410415 Tyr Tyr Ser Tyr Ser Thr Lys Thr Ser Thr Tyr Glu Tyr Thr Asp Ile 420425 430 Pro Phe His Asn Gln Tyr Phe His Ile Ser Met Leu Asp Tyr Asn Ala435 440 445 Arg Asp Arg Ala Leu Tyr Ala Trp Asn Asn Gly His Gln Val LeuPhe 450 455 460 Asn Val Thr Leu Phe His Ile Ile Lys Thr Glu Asp Asp Thr465 470 475 28 589 PRT Homo sapiens 28 Met Trp Thr Ser Gly Arg Met SerAsn Ala Lys Asn Trp Leu Gly Leu 1 5 10 15 Gly Met Ser Leu Tyr Phe TrpGly Leu Met Asp Leu Thr Thr Thr Val 20 25 30 Leu Ser Asp Thr Pro Thr ProGln Gly Glu Leu Glu Ala Leu Leu Ser 35 40 45 Asp Lys Pro Gln Ser His GlnArg Thr Lys Arg Ser Trp Val Trp Asn 50 55 60 Gln Phe Phe Val Leu Glu GluTyr Thr Gly Thr Asp Pro Leu Tyr Val 65 70 75 80 Gly Lys Leu His Ser AspMet Asp Arg Gly Asp Gly Ser Ile Lys Tyr 85 90 95 Ile Leu Ser Gly Glu GlyAla Gly Ile Val Phe Thr Ile Asp Asp Thr 100 105 110 Thr Gly Asp Ile HisAla Ile Gln Arg Leu Asp Arg Glu Glu Arg Ala 115 120 125 Gln Tyr Thr LeuArg Ala Gln Ala Leu Asp Arg Arg Thr Gly Arg Pro 130 135 140 Met Glu ProGlu Ser Glu Phe Ile Ile Lys Ile Gln Asp Ile Asn Asp 145 150 155 160 AsnGlu Pro Lys Phe Leu Asp Gly Pro Tyr Val Ala Thr Val Pro Glu 165 170 175Met Ser Pro Val Gly Thr Ser Val Ile Gln Val Thr Ala Thr Asp Ala 180 185190 Asp Asp Pro Thr Tyr Gly Asn Ser Ala Arg Val Val Tyr Ser Ile Leu 195200 205 Gln Gly Gln Pro Tyr Phe Ser Val Asp Ser Lys Thr Gly Val Ile Arg210 215 220 Thr Ala Leu Met Asn Met Asp Arg Glu Ala Lys Glu Tyr Tyr GluVal 225 230 235 240 Ile Ile Gln Ala Lys Asp Met Gly Gly Gln Leu Gly GlyLeu Ala Gly 245 250 255 Thr Thr Thr Val Asn Ile Thr Leu Ser Asp Val AsnAsp Asn Pro Pro 260 265 270 Arg Phe Pro Gln Lys His Tyr Gln Met Ser ValLeu Glu Ser Ala Pro 275 280 285 Ile Ser Ser Thr Val Gly Arg Val Phe AlaLys Asp Leu Asp Glu Gly 290 295 300 Ile Asn Ala Glu Met Lys Tyr Thr IleVal Asp Gly Asp Gly Ala Asp 305 310 315 320 Ala Phe Asp Ile Ser Thr AspPro Asn Phe Gln Val Gly Ile Ile Thr 325 330 335 Val Lys Lys Pro Leu SerPhe Glu Ser Lys Lys Ser Tyr Thr Leu Lys 340 345 350 Val Glu Gly Ala AsnPro His Leu Glu Met Arg Phe Leu Asn Leu Gly 355 360 365 Pro Phe Gln AspThr Thr Thr Val His Ile Ser Val Glu Asp Val Asp 370 375 380 Glu Pro ProVal Phe Glu Pro Gly Phe Tyr Phe Val Glu Val Pro Glu 385 390 395 400 AspVal Ala Ile Gly Thr Thr Ile Gln Ile Ile Ser Ala Lys Asp Pro 405 410 415Asp Val Thr Asn Asn Ser Ile Arg Tyr Ser Ile Asp Arg Ser Ser Asp 420 425430 Pro Gly Arg Phe Phe Tyr Val Asp Ile Thr Thr Gly Ala Leu Met Thr 435440 445 Ala Arg Pro Leu Asp Arg Glu Glu Phe Ser Trp His Asn Ile Thr Val450 455 460 Leu Ala Met Glu Met Asn Asn Pro Ser Gln Val Gly Ser Val ProVal 465 470 475 480 Thr Ile Lys Val Leu Asp Val Asn Asp Asn Ala Pro GluPhe Pro Arg 485 490 495 Phe Tyr Glu Ala Phe Val Cys Glu Asn Ala Lys AlaGly Gln Leu Ile 500 505 510 Gln Thr Val Ser Ala Val Asp Gln Asp Asp ProArg Asn Gly Gln His 515 520 525 Phe Tyr Tyr Ser Leu Ala Pro Glu Ala AlaAsn Asn Pro Asn Phe Thr 530 535 540 Ile Arg Asp Asn Gln Gly Asn Gln ValAsp Gly Trp Leu Ser Val Leu 545 550 555 560 Phe Tyr Ser Ile Gly Gln LeuLeu Trp Val Thr Val Leu Cys Lys Gln 565 570 575 Cys Gln Arg Leu Pro ValPro Tyr Gln Gln Gly Gly Cys 580 585 29 801 PRT Homo sapiens 29 Met TrpThr Ser Gly Arg Met Ser Asn Ala Lys Asn Trp Leu Gly Leu 1 5 10 15 GlyMet Ser Leu Tyr Phe Trp Gly Leu Met Asp Leu Thr Thr Thr Val 20 25 30 LeuSer Asp Thr Pro Thr Pro Gln Gly Glu Leu Glu Ala Leu Leu Ser 35 40 45 AspLys Pro Gln Ser His Gln Arg Thr Lys Arg Ser Trp Val Trp Asn 50 55 60 GlnPhe Phe Val Leu Glu Glu Tyr Thr Gly Thr Asp Pro Leu Tyr Val 65 70 75 80Gly Lys Leu His Ser Asp Met Asp Arg Gly Asp Gly Ser Ile Lys Tyr 85 90 95Ile Leu Ser Gly Glu Gly Ala Gly Ile Val Phe Thr Ile Asp Asp Thr 100 105110 Thr Gly Asp Ile His Ala Ile Gln Arg Leu Asp Arg Glu Glu Arg Ala 115120 125 Gln Tyr Thr Leu Arg Ala Gln Ala Leu Asp Arg Arg Thr Gly Arg Pro130 135 140 Met Glu Pro Glu Ser Glu Phe Ile Ile Lys Ile Gln Asp Ile AsnAsp 145 150 155 160 Asn Glu Pro Lys Phe Leu Asp Gly Pro Tyr Val Ala ThrVal Pro Glu 165 170 175 Met Ser Pro Val Gly Thr Ser Val Ile Gln Val ThrAla Thr Asp Ala 180 185 190 Asp Asp Pro Thr Tyr Gly Asn Ser Ala Arg ValVal Tyr Ser Ile Leu 195 200 205 Gln Gly Gln Pro Tyr Phe Ser Val Asp SerLys Thr Gly Val Ile Arg 210 215 220 Thr Ala Leu Met Asn Met Asp Arg GluAla Lys Glu Tyr Tyr Glu Val 225 230 235 240 Ile Ile Gln Ala Lys Asp MetGly Gly Gln Leu Gly Gly Leu Ala Gly 245 250 255 Thr Thr Thr Val Asn IleThr Leu Ser Asp Val Asn Asp Asn Pro Pro 260 265 270 Arg Phe Pro Gln LysHis Tyr Gln Met Ser Val Leu Glu Ser Ala Pro 275 280 285 Ile Ser Ser ThrVal Gly Arg Val Phe Ala Lys Asp Leu Asp Glu Gly 290 295 300 Ile Asn AlaGlu Met Lys Tyr Thr Ile Val Asp Gly Asp Gly Ala Asp 305 310 315 320 AlaPhe Asp Ile Ser Thr Asp Pro Asn Phe Gln Val Gly Ile Ile Thr 325 330 335Val Lys Lys Pro Leu Ser Phe Glu Ser Lys Lys Ser Tyr Thr Leu Lys 340 345350 Val Glu Gly Ala Asn Pro His Leu Glu Met Arg Phe Leu Asn Leu Gly 355360 365 Pro Phe Gln Asp Thr Thr Thr Val His Ile Ser Val Glu Asp Val Asp370 375 380 Glu Pro Pro Val Phe Glu Pro Gly Phe Tyr Phe Val Glu Val ProGlu 385 390 395 400 Asp Val Ala Ile Gly Thr Thr Ile Gln Ile Ile Ser AlaLys Asp Pro 405 410 415 Asp Val Thr Asn Asn Ser Ile Arg Tyr Ser Ile AspArg Ser Ser Asp 420 425 430 Pro Gly Arg Phe Phe Tyr Val Asp Ile Thr ThrGly Ala Leu Met Thr 435 440 445 Ala Arg Pro Leu Asp Arg Glu Glu Phe SerTrp His Asn Ile Thr Val 450 455 460 Leu Ala Met Glu Met Asn Asn Pro SerGln Val Gly Ser Val Pro Val 465 470 475 480 Thr Ile Lys Val Leu Asp ValAsn Asp Asn Ala Pro Glu Phe Pro Arg 485 490 495 Phe Tyr Glu Ala Phe ValCys Glu Asn Ala Lys Ala Gly Gln Leu Ile 500 505 510 Gln Thr Val Ser AlaVal Asp Gln Asp Asp Pro Arg Asn Gly Gln His 515 520 525 Phe Tyr Tyr SerLeu Ala Pro Glu Ala Ala Asn Asn Pro Asn Phe Thr 530 535 540 Ile Arg AspAsn Gln Asp Asn Thr Ala Arg Ile Leu Thr Arg Arg Ser 545 550 555 560 GlyPhe Arg Gln Gln Glu Gln Ser Val Phe His Leu Pro Ile Leu Ile 565 570 575Ala Asp Ser Gly Gln Pro Val Leu Ser Ser Thr Gly Thr Leu Thr Ile 580 585590 Gln Val Cys Ser Cys Asp Asp Asp Gly His Val Met Ser Cys Ser Pro 595600 605 Glu Ala Tyr Met Leu Pro Val Ser Leu Ser Arg Gly Ala Leu Ile Ala610 615 620 Ile Leu Ala Cys Ile Phe Val Leu Leu Val Leu Val Leu Leu IleLeu 625 630 635 640 Ser Met Arg Arg His Arg Lys Gln Pro Tyr Ile Ile AspAsp Glu Glu 645 650 655 Asn Ile His Glu Asn Ile Val Arg Tyr Asp Asp GluGly Gly Gly Glu 660 665 670 Glu Asp Thr Glu Ala Phe Asp Ile Ala Ala MetTrp Asn Pro Arg Glu 675 680 685 Ala Gln Ala Gly Ala Ala Pro Lys Thr ArgGln Asp Met Leu Pro Glu 690 695 700 Ile Glu Ser Leu Ser Arg Tyr Val ProGln Thr Cys Ala Val Asn Ser 705 710 715 720 Thr Val His Ser Tyr Val LeuAla Lys Leu Tyr Glu Ala Asp Met Asp 725 730 735 Leu Trp Ala Pro Pro PheAsp Ser Leu Gln Thr Tyr Met Phe Glu Gly 740 745 750 Asp Gly Ser Val AlaGly Ser Leu Ser Ser Leu Gln Ser Ala Thr Ser 755 760 765 Asp Ser Glu GlnSer Phe Asp Phe Leu Thr Asp Trp Gly Pro Arg Phe 770 775 780 Arg Lys LeuAla Glu Leu Tyr Gly Ala Ser Glu Gly Pro Ala Pro Leu 785 790 795 800 Trp30 287 PRT Homo sapiens 30 Met Ala Leu Gly Leu Leu Ile Ala Val Pro LeuLeu Leu Gln Ala Ala 1 5 10 15 Pro Pro Gly Ala Ala His Tyr Glu Met LeuGly Thr Cys Arg Met Ile 20 25 30 Cys Asp Pro Tyr Ser Val Ala Pro Ala GlyGly Pro Ala Gly Ala Lys 35 40 45 Ala Pro Pro Pro Gly Pro Ser Thr Ala AlaLeu Glu Val Met Gln Asp 50 55 60 Leu Ser Ala Asn Pro Pro Pro Pro Phe IleGln Gly Pro Lys Gly Asp 65 70 75 80 Pro Gly Arg Pro Gly Lys Pro Gly ProArg Gly Pro Pro Gly Glu Pro 85 90 95 Gly Pro Pro Gly Pro Arg Gly Pro ProGly Glu Lys Gly Asp Ser Gly 100 105 110 Arg Pro Gly Leu Pro Gly Leu GlnLeu Thr Thr Ser Ala Ala Gly Gly 115 120 125 Val Gly Val Val Ser Gly GlyThr Gly Gly Gly Gly Asp Thr Glu Gly 130 135 140 Glu Val Thr Ser Ala LeuSer Ala Ala Phe Ser Gly Pro Lys Ile Ala 145 150 155 160 Phe Tyr Val GlyLeu Lys Ser Pro His Glu Gly Tyr Glu Val Leu Lys 165 170 175 Phe Asp AspVal Val Thr Asn Leu Gly Asn His Tyr Asp Pro Thr Thr 180 185 190 Gly LysPhe Ser Cys Gln Val Arg Gly Ile Tyr Phe Phe Thr Tyr His 195 200 205 IleLeu Met Arg Gly Gly Asp Gly Thr Ser Met Trp Ala Asp Leu Cys 210 215 220Lys Asn Gly Gln Val Arg Ala Ser Ala Ile Ala Gln Asp Ala Asp Gln 225 230235 240 Asn Tyr Asp Tyr Ala Ser Asn Ser Val Val Leu His Leu Asp Ser Gly245 250 255 Asp Glu Val Tyr Val Lys Leu Asp Gly Gly Lys Ala His Gly GlyAsn 260 265 270 Asn Asn Lys Tyr Ser Thr Phe Ser Gly Phe Leu Leu Tyr ProAsp 275 280 285 31 159 PRT Homo sapiens 31 Met Lys Ala Trp Gly Thr ValVal Val Thr Leu Ala Thr Leu Met Val 1 5 10 15 Val Thr Val Asp Ala LysIle Tyr Glu Arg Cys Glu Leu Ala Ala Arg 20 25 30 Leu Glu Arg Ala Gly LeuAsn Gly Tyr Lys Gly Tyr Gly Val Gly Asp 35 40 45 Trp Leu Cys Met Ala HisTyr Glu Ser Gly Phe Asp Thr Ala Phe Val 50 55 60 Asp His Asn Pro Asp GlySer Ser Glu Tyr Gly Ile Phe Gln Leu Asn 65 70 75 80 Ser Ala Trp Trp CysAsp Asn Gly Ile Thr Pro Thr Lys Asn Leu Cys 85 90 95 His Met Asp Cys HisAsp Leu Leu Asn Arg His Ile Leu Asp Asp Ile 100 105 110 Arg Cys Ala LysGln Ile Val Ser Ser Gln Asn Gly Leu Ser Ala Trp 115 120 125 Thr Ser TrpArg Leu His Cys Ser Gly His Asp Leu Ser Glu Trp Leu 130 135 140 Lys GlyCys Asp Met His Val Lys Ile Asp Pro Lys Ile His Pro 145 150 155 32 220PRT Homo sapiens 32 Met Val Arg Asn Ile Phe Lys Thr Phe Pro Ser Val PheThr Gly Asn 1 5 10 15 Val Val Ser Gln Ser Ser Leu Thr Pro Leu Met ValAsn Gly Ile Leu 20 25 30 Gly Glu Ser Val Thr Leu Pro Leu Glu Phe Pro AlaGly Glu Lys Val 35 40 45 Asn Phe Ile Thr Trp Leu Phe Asn Glu Thr Ser LeuAla Phe Ile Val 50 55 60 Pro His Glu Thr Lys Ser Pro Glu Ile His Val ThrAsn Pro Lys Gln 65 70 75 80 Gly Lys Arg Leu Asn Phe Thr Gln Ser Tyr SerLeu Gln Leu Ser Asn 85 90 95 Leu Lys Met Glu Asp Thr Gly Ser Tyr Arg AlaGln Ile Ser Thr Lys 100 105 110 Thr Ser Ala Lys Leu Ser Ser Tyr Thr LeuArg Ile Leu Arg Gln Leu 115 120 125 Arg Asn Ile Gln Val Thr Asn His SerGln Leu Phe Gln Asn Met Thr 130 135 140 Cys Glu Leu His Leu Thr Cys SerVal Glu Asp Ala Asp Asp Asn Val 145 150 155 160 Ser Phe Arg Trp Glu AlaLeu Gly Asn Thr Leu Ser Ser Gln Pro Asn 165 170 175 Leu Thr Val Ser TrpAsp Pro Arg Ile Ser Ser Glu Gln Asp Tyr Thr 180 185 190 Cys Ile Ala GluAsn Ala Val Ser Asn Leu Ser Phe Ser Val Ser Ala 195 200 205 Gln Lys LeuCys Glu Gly Asn Ser Leu Pro Gln Val 210 215 220 33 346 PRT Homo sapiens33 Met Thr Ala Ser Arg Ser Gln Ala Pro Val Phe Thr Ala Glu Ser Met 1 510 15 Leu Trp Leu Phe Gln Ser Leu Leu Phe Val Phe Cys Phe Gly Pro Gly 2025 30 Asn Val Val Ser Gln Ser Ser Leu Thr Pro Leu Met Val Asn Gly Ile 3540 45 Leu Gly Glu Ser Val Thr Leu Pro Leu Glu Phe Pro Ala Gly Glu Lys 5055 60 Val Asn Phe Ile Thr Trp Leu Phe Asn Glu Thr Ser Leu Ala Phe Ile 6570 75 80 Val Pro His Glu Thr Lys Ser Pro Glu Ile His Val Thr Asn Pro Lys85 90 95 Gln Gly Lys Arg Leu Asn Phe Thr Gln Ser Tyr Ser Leu Gln Leu Ser100 105 110 Asn Leu Lys Met Glu Asp Thr Gly Ser Tyr Arg Ala Gln Ile SerThr 115 120 125 Lys Thr Ser Ala Lys Leu Ser Ser Tyr Thr Leu Arg Ile LeuArg Gln 130 135 140 Leu Arg Asn Ile Gln Val Thr Asn His Ser Gln Leu PheGln Asn Met 145 150 155 160 Thr Cys Glu Leu His Leu Thr Cys Ser Val GluAsp Ala Asp Asp Asn 165 170 175 Val Ser Phe Arg Trp Glu Ala Leu Gly AsnThr Leu Ser Ser Gln Pro 180 185 190 Asn Leu Thr Val Ser Trp Asp Pro ArgIle Ser Ser Glu Gln Asp Tyr 195 200 205 Thr Cys Ile Ala Glu Asn Ala ValSer Asn Leu Ser Phe Ser Val Ser 210 215 220 Ala Gln Lys Leu Cys Glu AspVal Lys Ile Gln Tyr Thr Asp Thr Lys 225 230 235 240 Met Ile Leu Phe MetVal Ser Gly Ile Cys Ile Val Phe Gly Phe Ile 245 250 255 Ile Leu Leu LeuLeu Val Leu Arg Lys Arg Arg Asp Ser Leu Ser Leu 260 265 270 Ser Thr GlnArg Thr Gln Gly Pro Glu Ser Ala Arg Asn Leu Glu Tyr 275 280 285 Val SerVal Ser Pro Thr Asn Asn Thr Val Tyr Ala Ser Val Thr His 290 295 300 SerAsn Arg Glu Thr Glu Ile Trp Thr Pro Arg Glu Asn Asp Thr Ile 305 310 315320 Thr Ile Tyr Ser Thr Ile Asn His Ser Lys Glu Ser Lys Pro Thr Phe 325330 335 Ser Arg Ala Thr Ala Leu Asp Asn Val Val 340 345 34 1075 PRT Homosapiens 34 Met Gly Thr Ala Tyr Leu Cys Cys Pro Gln Val Leu Leu Leu LeuCys 1 5 10 15 Leu Pro Arg Arg Val Lys Leu Trp Ala Asp Thr Phe Gly GlyAsp Leu 20 25 30 Tyr Asn Thr Val Thr Lys Tyr Ser Gly Ser Leu Leu Leu GlnLys Lys 35 40 45 Tyr Lys Asp Val Glu Ser Ser Leu Lys Ile Glu Glu Val AspGly Leu 50 55 60 Glu Leu Val Arg Lys Phe Ser Glu Asp Met Glu Asn Met LeuArg Arg 65 70 75 80 Lys Val Glu Ala Val Gln Asn Leu Val Glu Ala Ala GluGlu Ala Asp 85 90 95 Leu Asn His Glu Phe Asn Glu Ser Leu Val Phe Asp TyrTyr Asn Ser 100 105 110 Val Leu Ile Asn Glu Arg Asp Glu Lys Gly Asn PheVal Glu Leu Gly 115 120 125 Ala Glu Phe Leu Leu Glu Ser Asn Ala His PheSer Asn Leu Pro Val 130 135 140 Asn Thr Ser Ile Ser Ser Val Gln Leu ProThr Asn Val Tyr Asn Lys 145 150 155 160 Asp Pro Asp Ile Leu Asn Gly ValTyr Met Ser Glu Ala Leu Asn Ala 165 170 175 Val Phe Val Glu Asn Phe GlnArg Asp Pro Thr Leu Thr Trp Gln Tyr 180 185 190 Phe Gly Ser Ala Thr GlyPhe Phe Arg Ile Tyr Pro Gly Ile Lys Trp 195 200 205 Thr Pro Asp Glu AsnGly Val Ile Thr Phe Asp Cys Arg Asn Arg Gly 210 215 220 Trp Tyr Ile GlnAla Ala Thr Ser Pro Lys Asp Ile Val Ile Leu Val 225 230 235 240 Asp ValSer Gly Ser Met Lys Gly Leu Arg Met Thr Ile Ala Lys His 245 250 255 ThrIle Thr Thr Ile Leu Asp Thr Leu Gly Glu Asn Asp Phe Ile Asn 260 265 270Ile Ile Ala Tyr Asn Asp Tyr Val His Tyr Ile Glu Pro Cys Phe Lys 275 280285 Gly Ile Leu Val Gln Ala Asp Arg Asp Asn Arg Glu His Phe Lys Leu 290295 300 Leu Val Glu Glu Leu Met Val Lys Gly Val Gly Val Val Asp Gln Ala305 310 315 320 Leu Arg Glu Ala Phe Gln Ile Leu Lys Gln Phe Gln Glu AlaLys Gln 325 330 335 Gly Ser Leu Cys Asn Gln Ala Ile Met Leu Ile Ser AspGly Ala Val 340 345 350 Glu Asp Tyr Glu Pro Val Phe Glu Lys Tyr Asn TrpPro Asp Cys Lys 355 360 365 Val Arg Val Phe Thr Tyr Leu Ile Gly Arg GluVal Ser Phe Ala Asp 370 375 380 Arg Met Lys Trp Ile Ala Cys Asn Asn LysGly Tyr Tyr Thr Gln Ile 385 390 395 400 Ser Thr Leu Ala Asp Thr Gln GluAsn Val Met Glu Tyr Leu His Val 405 410 415 Leu Ser Arg Pro Met Val IleAsn His Asp His Asp Ile Ile Trp Thr 420 425 430 Glu Ala Tyr Met Asp SerLys Leu Leu Ser Ser Gln Ala Gln Ser Leu 435 440 445 Thr Leu Leu Thr ThrVal Ala Met Pro Val Phe Ser Lys Lys Asn Glu 450 455 460 Thr Arg Ser HisGly Ile Leu Leu Gly Val Val Gly Ser Asp Val Ala 465 470 475 480 Leu ArgGlu Leu Met Lys Leu Ala Pro Arg Tyr Lys Leu Gly Val His 485 490 495 GlyTyr Ala Phe Leu Asn Thr Asn Asn Gly Tyr Ile Leu Ser His Pro 500 505 510Asp Leu Arg Pro Leu Tyr Arg Glu Gly Lys Lys Leu Lys Pro Lys Pro 515 520525 Asn Tyr Asn Ser Val Asp Leu Ser Glu Val Glu Trp Glu Asp Gln Ala 530535 540 Glu Ser Leu Arg Thr Ala Met Ile Asn Arg Glu Thr Gly Thr Leu Ser545 550 555 560 Met Asp Val Lys Val Pro Met Asp Lys Gly Lys Arg Val LeuPhe Leu 565 570 575 Thr Asn Asp Tyr Phe Phe Thr Asp Ile Ser Asp Thr ProPhe Ser Leu 580 585 590 Gly Val Val Leu Ser Arg Gly His Gly Glu Tyr IleLeu Leu Gly Asn 595 600 605 Thr Ser Val Glu Glu Gly Leu His Asp Leu LeuHis Pro Asp Leu Ala 610 615 620 Leu Ala Gly Asp Trp Ile Tyr Cys Ile ThrAsp Ile Asp Pro Asp His 625 630 635 640 Arg Lys Leu Ser Gln Leu Glu AlaMet Ile Arg Phe Leu Thr Arg Lys 645 650 655 Asp Pro Asp Leu Glu Cys AspGlu Glu Leu Val Arg Glu Val Leu Phe 660 665 670 Asp Ala Val Val Thr AlaPro Met Glu Ala Tyr Trp Thr Ala Leu Ala 675 680 685 Leu Asn Met Ser GluGlu Ser Glu His Val Val Asp Met Ala Phe Leu 690 695 700 Gly Thr Arg AlaGly Leu Leu Arg Ser Ser Leu Phe Val Gly Ser Glu 705 710 715 720 Lys ValSer Asp Arg Lys Phe Leu Thr Pro Glu Asp Glu Ala Ser Val 725 730 735 PheThr Leu Asp Arg Phe Pro Leu Trp Tyr Arg Gln Ala Ser Glu His 740 745 750Pro Ala Gly Ser Phe Val Phe Asn Leu Arg Trp Ala Glu Gly Pro Glu 755 760765 Ser Ala Gly Glu Pro Met Val Val Thr Ala Ser Thr Ala Val Ala Val 770775 780 Thr Val Asp Lys Arg Thr Ala Ile Ala Ala Ala Ala Gly Val Gln Met785 790 795 800 Lys Leu Glu Phe Leu Gln Arg Lys Phe Trp Ala Ala Thr ArgGln Cys 805 810 815 Ser Thr Val Asp Gly Pro Cys Thr Gln Ser Cys Glu AspSer Asp Leu 820 825 830 Asp Cys Phe Val Ile Asp Asn Asn Gly Phe Ile LeuIle Ser Lys Arg 835 840 845 Ser Arg Glu Thr Gly Arg Phe Leu Gly Glu ValAsp Gly Ala Val Leu 850 855 860 Thr Gln Leu Leu Ser Met Gly Val Phe SerGln Val Thr Met Tyr Asp 865 870 875 880 Tyr Gln Ala Met Cys Lys Pro SerSer His His His Ser Ala Ala Gln 885 890 895 Pro Leu Val Ser Pro Ile SerAla Phe Leu Thr Ala Thr Arg Trp Leu 900 905 910 Leu Gln Glu Leu Val LeuPhe Leu Leu Glu Trp Ser Val Trp Gly Ser 915 920 925 Trp Tyr Asp Arg GlyAla Glu Ala His Lys His Lys Lys Gln Asp Pro 930 935 940 Leu Gln Pro CysAsp Thr Glu Tyr Pro Val Phe Val Tyr Gln Pro Ala 945 950 955 960 Ile ArgGlu Ala Asn Gly Ile Val Glu Cys Gly Pro Cys Gln Lys Val 965 970 975 PheVal Val Gln Gln Ile Pro Asn Ser Asn Leu Leu Leu Leu Val Thr 980 985 990Asp Pro Thr Phe Cys Arg Met Gly Ser Gly Pro Glu Ile Leu Thr Leu 995 10001005 Thr Val Ala Ser Ala His Asn Ala Ser Val Lys Cys Asp Arg Met Arg1010 1015 1020 Ser Gln Lys Leu Arg Arg Arg Pro Asp Ser Cys His Ala PheHis Pro 1025 1030 1035 1040 Glu Glu Asn Ala Gln Asp Cys Gly Gly Ala SerAsp Thr Ser Ala Ser 1045 1050 1055 Pro Pro Leu Leu Leu Leu Pro Val CysAla Trp Gly Leu Leu Pro Gln 1060 1065 1070 Leu Leu Arg 1075 35 1114 PRTHomo sapiens 35 Met Pro Ala Thr Pro Asn Phe Leu Ala Asn Pro Ser Ser SerSer Arg 1 5 10 15 Trp Ile Pro Leu Gln Pro Met Pro Val Ala Trp Ala PheVal Gln Lys 20 25 30 Thr Ser Ala Leu Leu Trp Leu Leu Leu Leu Gly Thr SerLeu Ser Pro 35 40 45 Ala Trp Gly Gln Ala Lys Ile Pro Leu Glu Thr Val LysLeu Trp Ala 50 55 60 Asp Thr Phe Gly Gly Asp Leu Tyr Asn Thr Val Thr LysTyr Ser Gly 65 70 75 80 Ser Leu Leu Leu Gln Lys Lys Tyr Lys Asp Val GluSer Ser Leu Lys 85 90 95 Ile Glu Glu Val Asp Gly Leu Glu Leu Val Arg LysPhe Ser Glu Asp 100 105 110 Met Glu Asn Met Leu Arg Arg Lys Val Glu AlaVal Gln Asn Leu Val 115 120 125 Glu Ala Ala Glu Glu Ala Asp Leu Asn HisGlu Phe Asn Glu Ser Leu 130 135 140 Val Phe Asp Tyr Tyr Asn Ser Val LeuIle Asn Glu Arg Asp Glu Lys 145 150 155 160 Gly Asn Phe Val Glu Leu GlyAla Glu Phe Leu Leu Glu Ser Asn Ala 165 170 175 His Phe Ser Asn Leu ProVal Asn Thr Ser Ile Ser Ser Val Gln Leu 180 185 190 Pro Thr Asn Val TyrAsn Lys Asp Pro Asp Ile Leu Asn Gly Val Tyr 195 200 205 Met Ser Glu AlaLeu Asn Ala Val Phe Val Glu Asn Phe Gln Arg Asp 210 215 220 Pro Thr LeuThr Trp Gln Tyr Phe Gly Ser Ala Thr Gly Phe Phe Arg 225 230 235 240 IleTyr Pro Gly Ile Lys Trp Thr Pro Asp Glu Asn Gly Val Ile Thr 245 250 255Phe Asp Cys Arg Asn Arg Gly Trp Tyr Ile Gln Ala Ala Thr Ser Pro 260 265270 Lys Asp Ile Val Ile Leu Val Asp Val Ser Gly Ser Met Lys Gly Leu 275280 285 Arg Met Thr Ile Ala Lys His Thr Ile Thr Thr Ile Leu Asp Thr Leu290 295 300 Gly Glu Asn Asp Phe Ile Asn Ile Ile Ala Tyr Asn Asp Tyr ValHis 305 310 315 320 Tyr Ile Glu Pro Cys Phe Lys Gly Ile Leu Val Gln AlaAsp Arg Asp 325 330 335 Asn Arg Glu His Phe Lys Leu Leu Val Glu Glu LeuMet Val Lys Gly 340 345 350 Val Gly Val Val Asp Gln Ala Leu Arg Glu AlaPhe Gln Ile Leu Lys 355 360 365 Gln Phe Gln Glu Ala Lys Gln Gly Ser LeuCys Asn Gln Ala Ile Met 370 375 380 Leu Ile Ser Asp Gly Ala Val Glu AspTyr Glu Pro Val Phe Glu Lys 385 390 395 400 Tyr Asn Trp Pro Asp Cys LysVal Arg Val Phe Thr Tyr Leu Ile Gly 405 410 415 Arg Glu Val Ser Phe AlaAsp Arg Met Lys Trp Ile Ala Cys Asn Asn 420 425 430 Lys Gly Tyr Tyr ThrGln Ile Ser Thr Leu Ala Asp Thr Gln Glu Asn 435 440 445 Val Met Glu TyrLeu His Val Leu Ser Arg Pro Met Val Ile Asn His 450 455 460 Asp His AspIle Ile Trp Thr Glu Ala Tyr Met Asp Ser Lys Leu Leu 465 470 475 480 SerSer Gln Ala Gln Ser Leu Thr Leu Leu Thr Thr Val Ala Met Pro 485 490 495Val Phe Ser Lys Lys Asn Glu Thr Arg Ser His Gly Ile Leu Leu Gly 500 505510 Val Val Gly Ser Asp Val Ala Leu Arg Glu Leu Met Lys Leu Ala Pro 515520 525 Arg Tyr Lys Leu Gly Val His Gly Tyr Ala Phe Leu Asn Thr Asn Asn530 535 540 Gly Tyr Ile Leu Ser His Pro Asp Leu Arg Pro Leu Tyr Arg GluGly 545 550 555 560 Lys Lys Leu Lys Pro Lys Pro Asn Tyr Asn Ser Val AspLeu Ser Glu 565 570 575 Val Glu Trp Glu Asp Gln Ala Glu Ser Leu Arg ThrAla Met Ile Asn 580 585 590 Arg Glu Thr Gly Thr Leu Ser Met Asp Val LysVal Pro Met Asp Lys 595 600 605 Gly Lys Arg Val Leu Phe Leu Thr Asn AspTyr Phe Phe Thr Asp Ile 610 615 620 Ser Asp Thr Pro Phe Ser Leu Gly ValVal Leu Ser Arg Gly His Gly 625 630 635 640 Glu Tyr Ile Leu Leu Gly AsnThr Ser Val Glu Glu Gly Leu His Asp 645 650 655 Leu Leu His Pro Asp LeuAla Leu Ala Gly Asp Trp Ile Tyr Cys Ile 660 665 670 Thr Asp Ile Asp ProAsp His Arg Lys Leu Ser Gln Leu Glu Ala Met 675 680 685 Ile Arg Phe LeuThr Arg Lys Asp Pro Asp Leu Glu Cys Asp Glu Glu 690 695 700 Leu Val ArgGlu Val Leu Phe Asp Ala Val Val Thr Ala Pro Met Glu 705 710 715 720 AlaTyr Trp Thr Ala Leu Ala Leu Asn Met Ser Glu Glu Ser Glu His 725 730 735Val Val Asp Met Ala Phe Leu Gly Thr Arg Ala Gly Leu Leu Arg Ser 740 745750 Ser Leu Phe Val Gly Ser Glu Lys Val Ser Asp Arg Lys Phe Leu Thr 755760 765 Pro Glu Asp Glu Ala Ser Val Phe Thr Leu Asp Arg Phe Pro Leu Trp770 775 780 Tyr Arg Gln Ala Ser Glu His Pro Ala Gly Ser Phe Val Phe AsnLeu 785 790 795 800 Arg Trp Ala Glu Gly Pro Glu Ser Ala Gly Glu Pro MetVal Val Thr 805 810 815 Ala Ser Thr Ala Val Ala Val Thr Val Asp Lys ArgThr Ala Ile Ala 820 825 830 Ala Ala Ala Gly Val Gln Met Lys Leu Glu PheLeu Gln Arg Lys Phe 835 840 845 Trp Ala Ala Thr Arg Gln Cys Ser Thr ValAsp Gly Pro Cys Thr Gln 850 855 860 Ser Cys Glu Asp Ser Asp Leu Asp CysPhe Val Ile Asp Asn Asn Gly 865 870 875 880 Phe Ile Leu Ile Ser Lys ArgSer Arg Glu Thr Gly Arg Phe Leu Gly 885 890 895 Glu Val Asp Gly Ala ValLeu Thr Gln Leu Leu Ser Met Gly Val Phe 900 905 910 Ser Gln Val Thr MetTyr Asp Tyr Gln Ala Met Cys Lys Pro Ser Ser 915 920 925 His His His SerAla Ala Gln Pro Leu Val Ser Pro Ile Ser Ala Phe 930 935 940 Leu Thr AlaThr Arg Trp Leu Leu Gln Glu Leu Val Leu Phe Leu Leu 945 950 955 960 GluTrp Ser Val Trp Gly Ser Trp Tyr Asp Arg Gly Ala Glu Ala His 965 970 975Lys His Lys Lys Gln Asp Pro Leu Gln Pro Cys Asp Thr Glu Tyr Pro 980 985990 Val Phe Val Tyr Gln Pro Ala Ile Arg Glu Ala Asn Gly Ile Val Glu 9951000 1005 Cys Gly Pro Cys Gln Lys Val Phe Val Val Gln Gln Ile Pro AsnSer 1010 1015 1020 Asn Leu Leu Leu Leu Val Thr Asp Pro Thr Phe Cys ArgMet Gly Ser 1025 1030 1035 1040 Gly Pro Glu Ile Leu Thr Leu Thr Val AlaSer Ala His Asn Ala Ser 1045 1050 1055 Val Lys Cys Asp Arg Met Arg SerGln Lys Leu Arg Arg Arg Pro Asp 1060 1065 1070 Ser Cys His Ala Phe HisPro Glu Glu Asn Ala Gln Asp Cys Gly Gly 1075 1080 1085 Ala Ser Asp ThrSer Ala Ser Pro Pro Leu Leu Leu Leu Pro Val Cys 1090 1095 1100 Ala TrpGly Leu Leu Pro Gln Leu Leu Arg 1105 1110 36 128 PRT Homo sapiens 36 MetAla Arg Ile Leu Leu Leu Phe Leu Pro Gly Leu Val Ala Val Cys 1 5 10 15Ala Val His Gly Ile Phe Met Asp Arg Leu Ala Ser Lys Lys Leu Cys 20 25 30Ala Asp Asp Glu Cys Val Tyr Thr Ile Ser Leu Ala Ser Ala Gln Glu 35 40 45Asp Tyr Asn Ala Pro Asp Cys Arg Phe Ile Asn Val Lys Lys Gly Gln 50 55 60Gln Ile Tyr Val Tyr Ser Lys Leu Val Lys Glu Asn Gly Ala Gly Glu 65 70 7580 Phe Trp Ala Gly Ser Val Tyr Gly Asp Gly Gln Asp Glu Met Gly Val 85 9095 Val Gly Tyr Phe Pro Arg Asn Leu Val Lys Glu Gln Arg Val Tyr Gln 100105 110 Glu Ala Thr Lys Glu Val Pro Thr Thr Asp Ile Asp Phe Phe Cys Glu115 120 125 37 215 PRT Homo sapiens 37 Met Gly Leu Thr Trp Ile Leu ValThr Ile Leu Leu Gly Gly Pro Gly 1 5 10 15 Val Gly Leu Pro Arg Ile GlnGln Phe Phe Thr Ser Pro Glu Asn Ser 20 25 30 Val Thr Ala Glu Pro Arg AlaArg Lys Tyr Lys Cys Gly Leu Pro Gln 35 40 45 Pro Cys Pro Glu Glu His LeuSer Phe Arg Ile Val Ser Gly Ala Ala 50 55 60 Asn Val Ile Gly Pro Lys IleCys Leu Glu Asp Lys Met Leu Met Ser 65 70 75 80 Ser Val Lys Asp Asn ValGly Arg Gly Leu Asn Ile Ala Leu Val Asn 85 90 95 Gly Val Ser Gly Glu LeuLeu Glu Ala Arg Ala Phe Asp Met Trp Ala 100 105 110 Gly Asp Val Asn AspLeu Leu Lys Phe Ile Arg Pro Leu His Glu Gly 115 120 125 Thr Leu Val PheVal Ala Ser Tyr Asp Asp Pro Ala Thr Lys Met Asn 130 135 140 Glu Glu ThrArg Lys Leu Phe Ser Glu Leu Gly Ser Arg Asn Ala Lys 145 150 155 160 AspLeu Ala Phe Arg Asp Ser Trp Val Phe Val Gly Ala Lys Gly Val 165 170 175Gln Asn Lys Ser Pro Phe Glu Gln His Met Lys Asn Ser Lys His Thr 180 185190 Asn Lys Tyr Glu Gly Trp Pro Glu Ala Leu Glu Met Glu Gly Cys Ile 195200 205 Pro Arg Arg Ser Ile Ala Gly 210 215 38 230 PRT Homo sapiens 38Met Arg Leu Ala Gly Pro Leu Arg Ile Val Ala Leu Ile Ile Ile Met 1 5 1015 Gly Leu Thr Trp Ile Leu Val Thr Ile Leu Leu Gly Gly Pro Gly Val 20 2530 Gly Leu Pro Arg Ile Gln Gln Phe Phe Thr Ser Pro Glu Asn Ser Val 35 4045 Thr Ala Glu Pro Arg Ala Arg Lys Tyr Lys Cys Gly Leu Pro Gln Pro 50 5560 Cys Pro Glu Glu His Leu Ser Phe Arg Ile Val Ser Gly Ala Ala Asn 65 7075 80 Val Ile Gly Pro Lys Ile Cys Leu Glu Asp Lys Met Leu Met Ser Ser 8590 95 Val Lys Asp Asn Val Gly Arg Gly Leu Asn Ile Ala Leu Val Asn Gly100 105 110 Val Ser Gly Glu Leu Leu Glu Ala Arg Ala Phe Asp Met Trp AlaGly 115 120 125 Asp Val Asn Asp Leu Leu Lys Phe Ile Arg Pro Leu His GluGly Thr 130 135 140 Leu Val Phe Val Ala Ser Tyr Asp Asp Pro Ala Thr LysMet Asn Glu 145 150 155 160 Glu Thr Arg Lys Leu Phe Ser Glu Leu Gly SerArg Asn Ala Lys Asp 165 170 175 Leu Ala Phe Arg Asp Ser Trp Val Phe ValGly Ala Lys Gly Val Gln 180 185 190 Asn Lys Ser Pro Phe Glu Gln His MetLys Asn Ser Lys His Thr Asn 195 200 205 Lys Tyr Glu Gly Trp Pro Glu AlaLeu Glu Met Glu Gly Cys Ile Pro 210 215 220 Arg Arg Ser Ile Ala Gly 225230 39 436 PRT Homo sapiens 39 Met Gln Gly Thr Pro Gly Gly Gly Thr ArgPro Gly Pro Ser Pro Val 1 5 10 15 Asp Arg Arg Thr Leu Leu Val Phe SerPhe Ile Leu Ala Ala Ala Leu 20 25 30 Gly Gln Met Asn Phe Thr Gly Asp GlnVal Leu Arg Val Leu Ala Lys 35 40 45 Asp Glu Lys Gln Leu Ser Leu Leu GlyAsp Leu Glu Gly Leu Lys Pro 50 55 60 Gln Lys Val Asp Phe Trp Arg Gly ProAla Arg Pro Ser Leu Pro Val 65 70 75 80 Asp Met Arg Val Pro Phe Ser GluLeu Lys Asp Ile Lys Ala Tyr Leu 85 90 95 Glu Ser His Gly Leu Ala Tyr SerIle Met Ile Lys Asp Ile Gln Val 100 105 110 Leu Leu Asp Glu Glu Arg GlnAla Met Ala Lys Ser Arg Arg Leu Glu 115 120 125 Arg Ser Thr Asn Ser PheSer Tyr Ser Ser Tyr His Thr Leu Glu Glu 130 135 140 Ile Tyr Ser Trp IleAsp Asn Phe Val Met Glu His Ser Asp Ile Val 145 150 155 160 Ser Lys IleGln Ile Gly Asn Ser Phe Glu Asn Gln Ser Ile Leu Val 165 170 175 Leu LysPhe Ser Thr Gly Gly Ser Arg His Pro Ala Ile Trp Ile Asp 180 185 190 ThrGly Ile His Ser Arg Glu Trp Ile Thr His Ala Thr Gly Ile Trp 195 200 205Thr Ala Asn Lys Ile Val Ser Asp Tyr Gly Lys Asp Arg Val Leu Thr 210 215220 Asp Ile Leu Asn Ala Met Asp Ile Phe Ile Glu Leu Val Thr Asn Pro 225230 235 240 Asp Gly Phe Ala Phe Thr His Ser Met Asn Arg Leu Trp Arg LysAsn 245 250 255 Lys Ser Ile Arg Pro Gly Ile Phe Cys Ile Gly Val Asp LeuAsn Arg 260 265 270 Asn Trp Lys Ser Gly Phe Gly Gly Asn Gly Ser Asn SerAsn Pro Cys 275 280 285 Ser Glu Thr Tyr His Gly Pro Ser Pro Gln Ser GluPro Glu Val Ala 290 295 300 Ala Ile Val Asn Phe Ile Thr Ala His Gly AsnPhe Lys Ala Leu Ile 305 310 315 320 Ser Ile His Ser Tyr Ser Gln Met LeuMet Tyr Pro Tyr Gly Arg Leu 325 330 335 Leu Glu Pro Val Ser Asn Gln ArgGlu Leu Tyr Asp Leu Ala Lys Asp 340 345 350 Ala Val Glu Ala Leu Tyr LysVal His Gly Ile Glu Tyr Ile Phe Gly 355 360 365 Ser Ile Ser Thr Thr LeuTyr Val Ala Ser Gly Ile Thr Val Asp Trp 370 375 380 Ala Tyr Asp Ser GlyIle Lys Tyr Ala Phe Ser Phe Glu Leu Arg Asp 385 390 395 400 Thr Gly GlnTyr Gly Phe Leu Leu Pro Ala Thr Gln Ile Ile Pro Thr 405 410 415 Ala GlnGlu Thr Trp Met Ala Leu Arg Thr Ile Met Glu His Thr Leu 420 425 430 AsnHis Pro Tyr 435 40 419 PRT Homo sapiens 40 Met Arg Thr Leu Leu Val PheSer Phe Ile Leu Ala Ala Ala Leu Gly 1 5 10 15 Gln Met Asn Phe Thr GlyAsp Gln Val Leu Arg Val Leu Ala Lys Asp 20 25 30 Glu Lys Gln Leu Ser LeuLeu Gly Asp Leu Glu Gly Leu Lys Pro Gln 35 40 45 Lys Val Asp Phe Trp ArgGly Pro Ala Arg Pro Ser Leu Pro Val Asp 50 55 60 Met Arg Val Pro Phe SerGlu Leu Lys Asp Ile Lys Ala Tyr Leu Glu 65 70 75 80 Ser His Gly Leu AlaTyr Ser Ile Met Ile Lys Asp Ile Gln Val Leu 85 90 95 Leu Asp Glu Glu ArgGln Ala Met Ala Lys Ser Arg Arg Leu Glu Arg 100 105 110 Ser Thr Asn SerPhe Ser Tyr Ser Ser Tyr His Thr Leu Glu Glu Ile 115 120 125 Tyr Ser TrpIle Asp Asn Phe Val Met Glu His Ser Asp Ile Val Ser 130 135 140 Lys IleGln Ile Gly Asn Ser Phe Glu Asn Gln Ser Ile Leu Val Leu 145 150 155 160Lys Phe Ser Thr Gly Gly Ser Arg His Pro Ala Ile Trp Ile Asp Thr 165 170175 Gly Ile His Ser Arg Glu Trp Ile Thr His Ala Thr Gly Ile Trp Thr 180185 190 Ala Asn Lys Ile Val Ser Asp Tyr Gly Lys Asp Arg Val Leu Thr Asp195 200 205 Ile Leu Asn Ala Met Asp Ile Phe Ile Glu Leu Val Thr Asn ProAsp 210 215 220 Gly Phe Ala Phe Thr His Ser Met Asn Arg Leu Trp Arg LysAsn Lys 225 230 235 240 Ser Ile Arg Pro Gly Ile Phe Cys Ile Gly Val AspLeu Asn Arg Asn 245 250 255 Trp Lys Ser Gly Phe Gly Gly Asn Gly Ser AsnSer Asn Pro Cys Ser 260 265 270 Glu Thr Tyr His Gly Pro Ser Pro Gln SerGlu Pro Glu Val Ala Ala 275 280 285 Ile Val Asn Phe Ile Thr Ala His GlyAsn Phe Lys Ala Leu Ile Ser 290 295 300 Ile His Ser Tyr Ser Gln Met LeuMet Tyr Pro Tyr Gly Arg Leu Leu 305 310 315 320 Glu Pro Val Ser Asn GlnArg Glu Leu Tyr Asp Leu Ala Lys Asp Ala 325 330 335 Val Glu Ala Leu TyrLys Val His Gly Ile Glu Tyr Ile Phe Gly Ser 340 345 350 Ile Ser Thr ThrLeu Tyr Val Ala Ser Gly Ile Thr Val Asp Trp Ala 355 360 365 Tyr Asp SerGly Ile Lys Tyr Ala Phe Ser Phe Glu Leu Arg Asp Thr 370 375 380 Gly GlnTyr Gly Phe Leu Leu Pro Ala Thr Gln Ile Ile Pro Thr Ala 385 390 395 400Gln Glu Thr Trp Met Ala Leu Arg Thr Ile Met Glu His Thr Leu Asn 405 410415 His Pro Tyr 41 119 PRT Homo sapiens 41 Met Trp Ser Leu Pro Pro SerArg Ala Leu Ser Cys Ala Pro Leu Leu 1 5 10 15 Leu Leu Phe Ser Phe GlnPhe Leu Val Thr Tyr Ala Trp Arg Phe Gln 20 25 30 Glu Glu Glu Glu Trp AsnAsp Gln Lys Gln Ile Ala Val Tyr Leu Pro 35 40 45 Pro Thr Leu Glu Phe AlaVal Tyr Thr Phe Asn Lys Gln Ser Lys Asp 50 55 60 Trp Tyr Ala Tyr Lys LeuVal Pro Val Leu Ala Ser Trp Lys Glu Gln 65 70 75 80 Val Asp Glu His IleLeu Phe Cys Thr Ser Val Gln His Arg Leu Leu 85 90 95 Ser Asp Gly Gln GlyTrp Gln Arg Val Gly Gln Gly Leu Thr Arg Thr 100 105 110 Pro Gly Ser ProPhe Val Val 115 42 148 PRT Homo sapiens 42 Met Ser Ser Pro Gln Arg ArgLys Ala Met Pro Trp Ala Leu Ser Leu 1 5 10 15 Leu Leu Met Gly Phe GlnLeu Leu Val Thr Tyr Ala Trp Cys Ser Glu 20 25 30 Glu Glu Met Gly Gly AsnAsn Lys Ile Val Gln Asp Pro Met Phe Leu 35 40 45 Ala Thr Val Glu Phe AlaLeu Asn Thr Phe Asn Val Gln Ser Lys Glu 50 55 60 Glu His Ala Tyr Arg LeuLeu Arg Val Leu Ser Ser Trp Arg Glu Asp 65 70 75 80 Ser Met Asp Arg LysMet Val Phe Ser Met Asn Leu Gln Leu Arg Gln 85 90 95 Thr Val Cys Arg LysPhe Glu Asp Asp Ile Asp Asn Cys Pro Phe Gln 100 105 110 Glu Ser Leu GluLeu Asn Asn Thr Phe Thr Cys Phe Phe Thr Ile Ser 115 120 125 Thr Arg ProTrp Met Thr Gln Phe Ser Leu Leu Asn Lys Thr Cys Leu 130 135 140 Glu GlyPhe His 145 43 898 PRT Homo sapiens 43 Met Arg Ala Ala Leu Trp Thr LeuGly Leu Gly Pro Leu Leu Leu Asn 1 5 10 15 Leu Trp Ala Val Pro Ile GlyGly Pro Gly Ala Leu Arg Leu Ala Tyr 20 25 30 Arg His Ser Thr Cys Asp GlyVal Val Leu Val Arg His His Gly Ala 35 40 45 Trp Gly Tyr Val Cys Asn GlnGlu Trp Thr Leu Ala Glu Ala Ser Val 50 55 60 Val Cys Arg Gln Leu Gly CysGly Pro Ala Val Gly Ala Pro Lys Tyr 65 70 75 80 Val Pro Leu Pro Gly GluMet Ala Gln Pro Trp Leu His Asn Val Ser 85 90 95 Cys Arg Gly Asn Glu SerSer Leu Trp Glu Cys Ser Leu Gly Ser Trp 100 105 110 Cys Gln Ser Pro CysPro His Ala Trp Val Val Val Ala Leu Cys Ser 115 120 125 Asn Gly Thr PheArg Glu Leu Arg Leu Val Lys Gly Arg Ser Pro Cys 130 135 140 Ala Gly LeuPro Glu Ile Arg Asn Val Asn Gly Val Asp Arg Leu Cys 145 150 155 160 ValLeu His Val Glu Glu Ala Met Val Phe Cys Arg Glu Leu Gly Cys 165 170 175Gly Pro Val Leu Gln Ala Pro Arg Arg Asp Val Gly Val Val Arg Lys 180 185190 Tyr Leu Ala Cys Arg Gly Thr Glu Pro Thr Ile Arg Ser Cys Arg Leu 195200 205 Asp Asn Asn Phe Arg Ser Gly Cys Asp Leu Arg Leu Asp Ala Glu Val210 215 220 Val Cys Ser Gly His Thr Glu Ala Arg Leu Val Gly Gly Glu HisPro 225 230 235 240 Cys Ala Gly Arg Leu Glu Val Thr Trp Gly Thr Val CysAsp Ala Ala 245 250 255 Leu Asp Leu Ala Thr Ala His Val Val Cys Arg GluLeu Gln Cys Gly 260 265 270 Ala Val Val Ser Thr Pro Glu Gly Ala Arg PheGly Arg Gly Ser Gly 275 280 285 Pro Val Trp Thr Glu Ala Phe Arg Cys AlaGly Asn Glu Ser Leu Leu 290 295 300 Phe His Cys Pro Arg Gly Arg Gly SerGln Cys Gly His Gly His Asp 305 310 315 320 Ala Gly Leu Arg Cys Ser GluPhe Arg Met Val Asn Gly Ser Ser Ser 325 330 335 Cys Glu Gly Arg Val GluPhe Gln Val Gln Gly Ser Trp Ala Pro Leu 340 345 350 Cys Ala Thr His TrpAsp Ile Ala Asp Ala Thr Val Leu Cys His Gln 355 360 365 Leu Asn Cys GlyAsn Ala Val Ala Ala Pro Gly Gly Gly His Phe Gly 370 375 380 Asp Gly AspAla Ala Ile Trp Pro Asp Ala Phe His Cys Glu Gly Thr 385 390 395 400 GluSer Tyr Leu Trp Asn Cys Pro Val Ser Thr Leu Gly Ala Pro Ala 405 410 415Cys Ala Pro Gly Asn Thr Ala Ser Ala Val Cys Ser Gly Leu Ala His 420 425430 Ala Leu Arg Leu Arg Glu Gly Gln Ser Arg Cys Asp Gly Arg Val Glu 435440 445 Val Ser Leu Asp Gly Val Trp Gly Arg Val Leu Asp Asp Ala Trp Asp450 455 460 Leu Arg Gly Ala Gly Val Val Cys Arg Gln Leu Gly Cys Arg GlyAla 465 470 475 480 Gln Gln Ala Tyr Asp Ala Pro Ala Pro Ser Arg Gly SerVal Gln Val 485 490 495 Ala Leu Ser Arg Val Arg Cys Leu Gly Thr Glu ThrArg Leu Thr Gln 500 505 510 Cys Asn Val Ser Ala Thr Leu Gln Glu Pro AlaGly Thr Ser Arg Asp 515 520 525 Ala Gly Val Val Cys Ser Gly Glu Val GlyThr Ala Ser Pro Met Ala 530 535 540 Arg Arg His Gly Ile Pro Gly Ala LeuThr Leu Ser Leu His Arg Glu 545 550 555 560 Pro Gln Gly Ala Ala Gly ArgGly Ala Gly Ala Leu His Gly Gly Ala 565 570 575 Trp Gly Thr Val Cys AspAsp Ala Trp Asp Leu Arg Asp Ala His Val 580 585 590 Val Cys Arg Gln LeuGly Cys Gly Arg Ala Leu Ser Ala Leu Gly Ala 595 600 605 Ala His Phe GlyAla Gly Ala Gly Arg Ile Trp Leu Asp Glu Leu Gly 610 615 620 Cys Gln GlyHis Glu Ser Ala Leu Trp Gln Cys Pro Ser Ala Gly Trp 625 630 635 640 GlyArg His Asp Trp Arg His Lys Glu Asp Ala Gly Val Phe Cys Ser 645 650 655Glu Ser Val Ala Leu Arg Leu Arg Gly Gly Thr Cys Cys Cys Ala Gly 660 665670 Trp Leu Asp Val Phe Tyr Asn Gly Thr Trp Gly Ala Met Cys Ser Asn 675680 685 Ala Leu Lys Asp Leu Ser Leu Ser Ile Ile Cys Lys Gln Leu Gly Cys690 695 700 Gly Val Trp Gly Val Gly Leu Ala Gly Glu Gln Ala Leu Pro LeuAla 705 710 715 720 Gly Thr Gly Thr Ala Trp Val Asp Asn Ile Glu Cys ArgArg Leu Pro 725 730 735 Asn Ser Thr Leu Trp Gln Cys Pro Ser His Pro TrpHis Pro His Ser 740 745 750 Cys Asp Leu Arg Glu Gln Val Trp Ile Thr CysAla Val Thr Ala Ala 755 760 765 Pro Phe Ala Glu Glu Gly Ala Leu Arg ValArg Gly Gly Glu Asp Arg 770 775 780 Cys Ser Gly Arg Val Glu Leu Trp HisAla Gly Ser Trp Gly Thr Val 785 790 795 800 Cys Asp Asp Gly Trp Asp LeuAla Asp Ala Glu Val Val Cys Arg Gln 805 810 815 Leu Gly Cys Gly Arg AlaVal Ala Ala Leu Gly Ala Ala Ala Phe Gly 820 825 830 Pro Gly Ser Gly ProVal Trp Leu Asp Glu Val Gly Cys Arg Gly Ser 835 840 845 Glu Ala Ser LeuTrp Gly Cys Pro Ala Glu Arg Trp Gly Arg Gly Asp 850 855 860 Arg Ala HisGlu Glu Asp Ala Gly Val Arg Cys Trp Gly Glu Trp Gly 865 870 875 880 AlaVal Gly Ser Arg Ser Trp Gly Arg Gln Arg Ala Leu Gly Trp Ser 885 890 895Gln Ser 44 426 PRT Homo sapiens 44 Met Ala Gly Leu Gly Phe Trp Gly HisPro Ala Gly Pro Leu Leu Leu 1 5 10 15 Leu Leu Leu Leu Val Leu Pro ProArg Ala Leu Pro Glu Gly Pro Leu 20 25 30 Val Phe Val Ala Leu Val Phe ArgHis Gly Asp Arg Ala Pro Leu Ala 35 40 45 Ser Tyr Pro Met Asp Pro His LysGlu Val Ala Ser Thr Leu Trp Pro 50 55 60 Arg Gly Leu Gly Gln Leu Thr ThrGlu Gly Val Arg Gln Gln Leu Glu 65 70 75 80 Leu Gly Arg Phe Leu Arg SerArg Tyr Glu Ala Phe Leu Ser Pro Glu 85 90 95 Tyr Arg Arg Glu Glu Val TyrIle Arg Ser Thr Asp Phe Asp Arg Thr 100 105 110 Leu Glu Ser Ala Gln AlaAsn Leu Ala Gly Leu Phe Pro Glu Ala Ala 115 120 125 Pro Gly Ser Pro GluAla Arg Trp Arg Pro Ile Pro Val His Thr Val 130 135 140 Pro Val Ala GluAsp Lys Leu Leu Arg Phe Pro Met Arg Ser Cys Pro 145 150 155 160 Arg TyrHis Glu Leu Leu Arg Glu Ala Thr Glu Ala Ala Glu Tyr Gln 165 170 175 GluAla Leu Glu Gly Trp Thr Gly Phe Leu Ser Arg Leu Glu Asn Phe 180 185 190Thr Gly Leu Ser Leu Val Gly Glu Pro Leu Arg Arg Ala Trp Lys Val 195 200205 Leu Asp Thr Leu Met Cys Gln Gln Ala His Gly Leu Pro Leu Pro Ala 210215 220 Trp Ala Ser Pro Asp Val Leu Arg Thr Leu Ala Gln Ile Ser Ala Leu225 230 235 240 Asp Ile Gly Ala His Val Gly Pro Pro Arg Ala Ala Glu LysAla Gln 245 250 255 Leu Thr Gly Gly Ile Leu Leu Asn Ala Ile Leu Ala AsnPhe Ser Arg 260 265 270 Val Gln Arg Leu Gly Leu Pro Leu Lys Met Val MetTyr Ser Ala His 275 280 285 Asp Ser Thr Leu Leu Ala Leu Gln Gly Ala LeuGly Leu Tyr Asp Gly 290 295 300 His Thr Pro Pro Tyr Ala Ala Cys Leu GlyPhe Glu Phe Arg Lys His 305 310 315 320 Leu Gly Asn Pro Ala Lys Asp GlyGly Asn Val Thr Val Ser Leu Phe 325 330 335 Tyr Arg Asn Asp Ser Ala HisLeu Pro Leu Pro Leu Ser Leu Pro Gly 340 345 350 Cys Pro Ala Pro Cys ProLeu Gly Arg Phe Tyr Gln Leu Thr Ala Pro 355 360 365 Ala Arg Pro Pro AlaHis Gly Val Ser Cys His Gly Pro Tyr Glu Ala 370 375 380 Ala Ile Pro ProAla Pro Val Val Pro Leu Leu Ala Gly Ala Val Ala 385 390 395 400 Val LeuVal Ala Leu Ser Leu Gly Leu Gly Leu Leu Ala Trp Arg Pro 405 410 415 GlyCys Leu Arg Ala Leu Gly Gly Pro Val 420 425 45 475 PRT Homo sapiens 45Met Leu Ala Ala Ser Ile Phe Arg Pro Thr Leu Leu Leu Cys Trp Leu 1 5 1015 Ala Ala Pro Trp Pro Thr Gln Pro Glu Ser Leu Phe His Ser Arg Asp 20 2530 Arg Ser Asp Leu Glu Pro Ser Pro Leu Arg Gln Ala Lys Pro Ile Ala 35 4045 Asp Leu His Ala Ala Gln Arg Phe Leu Ser Arg Tyr Gly Trp Ser Gly 50 5560 Val Trp Ala Ala Trp Gly Pro Ser Pro Glu Gly Pro Pro Glu Thr Pro 65 7075 80 Lys Gly Ala Ala Leu Ala Glu Ala Val Arg Arg Phe Gln Arg Ala Asn 8590 95 Ala Leu Pro Ala Ser Gly Glu Leu Asp Ala Ala Thr Leu Ala Ala Met100 105 110 Asn Arg Pro Arg Cys Gly Val Pro Asp Met Arg Pro Pro Pro ProSer 115 120 125 Ala Pro Pro Ser Pro Pro Gly Pro Pro Pro Arg Ala Arg SerArg Arg 130 135 140 Ser Pro Arg Ala Pro Leu Ser Leu Ser Arg Arg Gly TrpGln Pro Arg 145 150 155 160 Gly Tyr Pro Asp Gly Gly Ala Ala Gln Ala PheSer Lys Arg Thr Leu 165 170 175 Ser Trp Arg Leu Leu Gly Glu Ala Leu SerSer Gln Leu Ser Val Ala 180 185 190 Asp Gln Arg Arg Ile Val Ala Leu AlaPhe Arg Met Trp Ser Glu Val 195 200 205 Thr Pro Leu Asp Phe Arg Glu AspLeu Ala Ala Pro Gly Ala Ala Val 210 215 220 Asp Ile Lys Leu Gly Phe GlyArg Gly Ser Cys Glu Gly Ser Phe Asp 225 230 235 240 Thr Ala Phe Asp TrpIle Arg Lys Glu Arg Asn Gln Tyr Gly Glu Val 245 250 255 Met Val Arg PheSer Thr Tyr Phe Phe Arg Asn Ser Trp Tyr Trp Leu 260 265 270 Tyr Glu AsnArg Asn Asn Arg Thr Arg Tyr Gly Asp Pro Ile Gln Ile 275 280 285 Leu ThrGly Trp Pro Gly Ile Pro Thr His Asn Ile Asp Ala Phe Val 290 295 300 HisIle Trp Thr Trp Lys Arg Asp Glu Arg Tyr Phe Phe Gln Gly Asn 305 310 315320 Gln Tyr Trp Arg Tyr Asp Ser Asp Lys Asp Gln Ala Leu Thr Glu Asp 325330 335 Glu Gln Gly Lys Ser Tyr Pro Lys Leu Ile Ser Glu Gly Phe Pro Gly340 345 350 Ile Pro Ser Pro Leu Asp Thr Ala Phe Tyr Asp Arg Arg Gln LysLeu 355 360 365 Ile Tyr Phe Phe Lys Glu Ser Leu Val Phe Ala Phe Asp ValAsn Arg 370 375 380 Asn Arg Val Leu Asn Ser Tyr Pro Lys Arg Ile Thr GluVal Phe Pro 385 390 395 400 Ala Val Ile Pro Gln Asn His Pro Phe Arg AsnIle Asp Ser Ala Tyr 405 410 415 Tyr Ser Tyr Ala Tyr Asn Ser Ile Phe PhePhe Lys Gly Asn Ala Tyr 420 425 430 Trp Lys Val Val Asn Asp Lys Asp LysGln Gln Asn Ser Trp Leu Pro 435 440 445 Ala Asn Gly Leu Phe Pro Lys LysPhe Ile Ser Glu Lys Trp Phe Asp 450 455 460 Val Cys Asp Val His Ile SerThr Leu Asn Met 465 470 475 46 529 PRT Homo sapiens 46 Met Leu Ala AlaSer Ile Phe Arg Pro Thr Leu Leu Leu Cys Trp Leu 1 5 10 15 Ala Ala ProTrp Pro Thr Gln Pro Glu Ser Leu Phe His Ser Arg Asp 20 25 30 Arg Ser AspLeu Glu Pro Ser Pro Leu Arg Gln Ala Lys Pro Ile Ala 35 40 45 Asp Leu HisAla Ala Gln Arg Phe Leu Ser Arg Tyr Gly Trp Ser Gly 50 55 60 Val Trp AlaAla Trp Gly Pro Ser Pro Glu Gly Pro Pro Glu Thr Pro 65 70 75 80 Lys GlyAla Ala Leu Ala Glu Ala Val Arg Arg Phe Gln Arg Ala Asn 85 90 95 Ala LeuPro Ala Ser Gly Glu Leu Asp Ala Ala Thr Leu Ala Ala Met 100 105 110 AsnArg Pro Arg Cys Gly Pro Arg Gly Tyr Pro Asp Gly Gly Ala Ala 115 120 125Gln Ala Phe Ser Lys Arg Thr Leu Ser Trp Arg Leu Leu Gly Glu Ala 130 135140 Leu Ser Ser Gln Leu Ser Val Ala Asp Gln Arg Arg Ile Val Ala Leu 145150 155 160 Ala Phe Arg Met Trp Ser Glu Val Thr Pro Leu Asp Phe Arg GluAsp 165 170 175 Leu Ala Ala Pro Gly Ala Ala Val Asp Ile Lys Leu Gly PheGly Arg 180 185 190 Gly Arg His Leu Gly Cys Pro Arg Ala Phe Asp Gly SerGly Gln Glu 195 200 205 Phe Ala His Ala Trp Arg Leu Gly Asp Ile His PheAsp Asp Asp Glu 210 215 220 His Phe Thr Pro Pro Thr Ser Asp Thr Gly IleSer Leu Leu Lys Val 225 230 235 240 Ala Val His Glu Ile Gly His Val LeuGly Leu Pro His Thr Tyr Arg 245 250 255 Thr Gly Ser Ile Met Gln Pro AsnTyr Ile Pro Gln Glu Pro Ala Phe 260 265 270 Glu Leu Asp Trp Ser Asp ArgLys Ala Ile Gln Lys Leu Tyr Gly Ser 275 280 285 Cys Glu Gly Ser Phe AspThr Ala Phe Asp Trp Ile Arg Lys Glu Arg 290 295 300 Asn Gln Tyr Gly GluVal Met Val Arg Phe Ser Thr Tyr Phe Phe Arg 305 310 315 320 Asn Ser TrpTyr Trp Leu Tyr Glu Asn Arg Asn Asn Arg Thr Arg Tyr 325 330 335 Gly AspPro Ile Gln Ile Leu Thr Gly Trp Pro Gly Ile Pro Thr His 340 345 350 AsnIle Asp Ala Phe Val His Ile Trp Thr Trp Lys Arg Asp Glu Arg 355 360 365Tyr Phe Phe Gln Gly Asn Gln Tyr Trp Arg Tyr Asp Ser Asp Lys Asp 370 375380 Gln Ala Leu Thr Glu Asp Glu Gln Gly Lys Ser Tyr Pro Lys Leu Ile 385390 395 400 Ser Glu Gly Phe Pro Gly Ile Pro Ser Pro Leu Asp Thr Ala PheTyr 405 410 415 Asp Arg Arg Gln Lys Leu Ile Tyr Phe Phe Lys Glu Ser LeuVal Phe 420 425 430 Ala Phe Asp Val Asn Arg Asn Arg Val Leu Asn Ser TyrPro Lys Arg 435 440 445 Ile Thr Glu Val Phe Pro Ala Val Ile Pro Gln AsnHis Pro Phe Arg 450 455 460 Asn Ile Asp Ser Ala Tyr Tyr Ser Tyr Ala TyrAsn Ser Ile Phe Phe 465 470 475 480 Phe Lys Gly Asn Ala Tyr Trp Lys ValVal Asn Asp Lys Asp Lys Gln 485 490 495 Gln Asn Ser Trp Leu Pro Ala AsnGly Leu Phe Pro Lys Lys Phe Ile 500 505 510 Ser Glu Lys Trp Phe Asp ValCys Asp Val His Ile Ser Thr Leu Asn 515 520 525 Met 47 402 PRT Homosapiens 47 Met Val Cys Ala Arg Ala Ala Leu Gly Pro Gly Ala Leu Trp AlaAla 1 5 10 15 Ala Trp Gly Val Leu Leu Leu Thr Ala Pro Ala Gly Ala GlnArg Gly 20 25 30 Arg Lys Lys Val Val His Val Leu Glu Gly Glu Ser Gly SerVal Val 35 40 45 Val Gln Thr Ala Pro Gly Gln Val Val Ser His Arg Gly GlyThr Ile 50 55 60 Val Leu Pro Cys Arg Tyr His Tyr Glu Ala Ala Ala His GlyHis Asp 65 70 75 80 Gly Val Arg Leu Lys Trp Thr Lys Val Val Asp Pro LeuAla Phe Thr 85 90 95 Asp Val Phe Val Ala Leu Gly Pro Gln His Arg Ala PheGly Ser Tyr 100 105 110 Arg Gly Arg Ala Glu Leu Gln Gly Asp Gly Pro GlyAsp Ala Ser Leu 115 120 125 Val Leu Arg Asn Val Thr Leu Gln Asp Tyr GlyArg Tyr Glu Cys Glu 130 135 140 Val Thr Asn Glu Leu Glu Asp Asp Ala GlyMet Val Lys Leu Asp Leu 145 150 155 160 Glu Gly Val Val Phe Pro Tyr HisPro Arg Gly Gly Arg Tyr Lys Leu 165 170 175 Thr Phe Ala Glu Ala Gln ArgAla Cys Ala Glu Gln Asp Gly Ile Leu 180 185 190 Ala Ser Ala Glu Gln LeuHis Ala Ala Trp Arg Asp Gly Leu Asp Trp 195 200 205 Cys Asn Ala Gly TrpLeu Arg Asp Gly Ser Val Gln Tyr Pro Val Asn 210 215 220 Arg Pro Arg GluPro Cys Gly Gly Leu Gly Gly Thr Gly Ser Ala Gly 225 230 235 240 Gly GlyGly Asp Ala Asn Gly Gly Leu Arg Asn Tyr Gly Tyr Arg His 245 250 255 AsnAla Glu Glu Arg Tyr Asp Ala Phe Cys Phe Thr Ser Asn Leu Pro 260 265 270Gly Arg Val Phe Phe Leu Lys Pro Leu Arg Pro Val Pro Phe Ser Gly 275 280285 Ala Ala Arg Ala Cys Ala Ala Arg Gly Ala Ala Val Ala Lys Val Gly 290295 300 Gln Leu Phe Ala Ala Trp Lys Leu Gln Leu Leu Asp Arg Cys Thr Ala305 310 315 320 Gly Trp Leu Ala Asp Gly Ser Ala Arg Tyr Pro Ile Val AsnPro Arg 325 330 335 Ala Arg Cys Gly Gly Arg Arg Pro Gly Val Arg Ser LeuGly Phe Pro 340 345 350 Asp Ala Thr Arg Arg Leu Phe Gly Val Tyr Cys TyrArg Ala Pro Gly 355 360 365 Ala Pro Asp Pro Ala Pro Gly Gly Trp Gly TrpGly Trp Ala Gly Gly 370 375 380 Gly Gly Trp Ala Gly Gly Ala Arg Asp ProAla Ala Trp Thr Pro Leu 385 390 395 400 His Val 48 441 PRT Homo sapiens48 Met Leu Pro Ala Arg Cys Ala Arg Leu Leu Thr Pro His Leu Leu Leu 1 510 15 Val Leu Val Gln Leu Ser Pro Ala Arg Gly His Arg Thr Thr Gly Pro 2025 30 Arg Phe Leu Ile Ser Asp Arg Asp Pro Gln Cys Asn Leu His Cys Ser 3540 45 Arg Thr Gln Pro Lys Pro Ile Cys Ala Ser Asp Gly Arg Ser Tyr Glu 5055 60 Ser Met Cys Glu Tyr Gln Arg Ala Lys Cys Arg Asp Pro Thr Leu Gly 6570 75 80 Val Val His Arg Gly Arg Cys Lys Asp Ala Gly Gln Ser Lys Cys Arg85 90 95 Leu Glu Arg Ala Gln Ala Leu Glu Gln Ala Lys Lys Pro Gln Glu Ala100 105 110 Val Phe Val Pro Glu Cys Gly Glu Asp Gly Ser Phe Thr Gln ValGln 115 120 125 Cys His Thr Tyr Thr Gly Tyr Cys Trp Cys Val Thr Pro AspGly Lys 130 135 140 Pro Ile Ser Gly Ser Ser Val Gln Asn Lys Thr Pro ValCys Ser Gly 145 150 155 160 Ser Val Thr Asp Lys Pro Leu Ser Gln Gly AsnSer Gly Arg Lys Asp 165 170 175 Asp Gly Ser Lys Pro Thr Pro Thr Met GluThr Gln Pro Val Phe Asp 180 185 190 Gly Asp Glu Ile Thr Ala Pro Thr LeuTrp Ile Lys His Leu Val Ile 195 200 205 Lys Asp Ser Lys Leu Asn Asn ThrAsn Ile Arg Asn Ser Glu Lys Val 210 215 220 Tyr Ser Cys Asp Gln Glu ArgGln Ser Ala Leu Glu Glu Ala Gln Gln 225 230 235 240 Asn Pro Arg Glu GlyIle Val Ile Pro Glu Cys Ala Pro Gly Gly Leu 245 250 255 Tyr Lys Pro ValGln Cys His Gln Ser Thr Gly Tyr Cys Trp Cys Val 260 265 270 Leu Val AspThr Gly Arg Pro Leu Pro Gly Thr Ser Thr Arg Tyr Val 275 280 285 Met ProSer Cys Glu Ser Asp Ala Arg Ala Lys Thr Thr Glu Ala Asp 290 295 300 AspPro Phe Lys Asp Arg Glu Leu Pro Gly Cys Pro Glu Gly Lys Lys 305 310 315320 Met Glu Phe Ile Thr Ser Leu Leu Asp Ala Leu Thr Thr Asp Met Val 325330 335 Gln Ala Ile Asn Ser Ala Ala Pro Thr Gly Gly Gly Arg Phe Ser Glu340 345 350 Pro Asp Pro Ser His Thr Leu Glu Glu Arg Val Val His Trp TyrPhe 355 360 365 Ser Gln Leu Asp Ser Asn Ser Ser Asn Asp Ile Asn Lys ArgGlu Met 370 375 380 Lys Pro Phe Lys Arg Tyr Val Lys Lys Lys Ala Lys ProLys Lys Cys 385 390 395 400 Ala Arg Arg Phe Thr Asp Tyr Cys Asp Leu AsnLys Asp Lys Val Ile 405 410 415 Ser Leu Pro Glu Leu Lys Gly Cys Leu GlyVal Ser Lys Glu Gly Gly 420 425 430 Ser Leu Gly Ser Phe Pro Gln Ala Lys435 440

What is claimed is:
 1. An isolated polypeptide selected from the groupconsisting of: (a) an isolated polypeptide encoded by a polynucleotidecomprising a sequence set forth in Table I; (b) an isolated polypeptidecomprising a polypeptide sequence set forth in Table I; and (c) apolypeptide sequence of a gene set forth in Table I.
 2. An isolatedpolynucleotide selected from the group consisting of: (a) an isolatedpolynucleotide comprising a polynucleotide sequence set forth in TableI; (b) an isolated polynucleotide of a gene set forth in Table I; (c) anisolated polynucleotide comprising a polynucleotide sequence encoding apolypeptide set forth in Table I; (d) an isolated polynucleotideencoding a polypeptide set forth in Table I; (e) a polynucleotide whichis an RNA equivalent of the polynucleotide of (a) to (d); or apolynucleotide sequence complementary to said isolated polynucleotide.3. An expression vector comprising a polynucleotide capable of producinga polypeptide of claim 1 when said expression vector is present in acompatible host cell.
 4. A process for producing a recombinant host cellwhich comprises the step of introducing an expression vector comprisinga polynucleotide capable of producing a polypeptide of claim 1 into acell such that the host cell, under appropriate culture conditions,produces said polypeptide.
 5. A recombinant host cell produced by theprocess of claim
 4. 6. A membrane of a recombinant host cell of claim 5expressing said polypeptide.
 7. A process for producing a polypeptidewhich comprises culturing a host cell of claim 5 under conditionssufficient for the production of said polypeptide and recovering saidpolypeptide from the culture.